|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 314-319
NEOPLASIA
From the INRS-Institut Armand-Frappier, Université du
Québec, Québec, Canada
Our recent finding that resistance to lymphoma cell metastasis in
intercellular adhesion molecule-1-(ICAM-1)-deficient mice was
manifested after homing suggested that the mechanism could involve the
capacity of ICAM-1 to induce, via leukocyte function-associated antigen-1 (LFA-1) signaling, the expression of new genes necessary for
migration and survival of lymphoma cells after homing. This hypothesis
would imply that lymphoma cells, on repeated metastatic cycles, would
acquire such a highly aggressive phenotype that they no longer require
contact with ICAM-1 at later stages of metastasis. We addressed this
question by generating highly aggressive lymphoma variants to determine
if increased tumorigenicity would allow lymphoma cells to grow into
tumors in ICAM-1-deficient mice. We found that on repeated in vivo
passages, a selective pressure favored the lymphoma cells that
constitutively express high levels of matrix metalloproteainse-9
(MMP-9), a gene associated with a poor clinical outcome in
non-Hodgkins's lymphoma. We further found that although the parent
lymphoma cells could not grow tumors in ICAM-1-deficient mice, the
aggressive lymphoma variants could. This indicates that, at late stages
of the disease, tumor cells with a high metastatic efficiency, encoded
by the repertoire of selected genes, no longer require some of the
signals normally delivered by cell adhesion molecules. In light of
these findings, the possibility of inhibiting dissemination of lymphoma
cells at the late stage of the disease by acting against cell adhesion molecules must be reconsidered. (Blood.
2000;95:314-319)
Cell adhesion molecules play a variety of roles during
distinct stages of metastasis. In the initial stage, down-regulation of
cell membrane integrins that interact with extracellular matrix proteins favors the spread of tumor cells by allowing them to detach
from the primary tumor and enter the circulation.1 In later
stages of metastasis, however, expression of adhesion molecules favoring intercellular contacts is necessary for the efficient spreading of metastatic cells.2-5 Although the latter was
first thought to provide specific homing signals for the invasion of target organs, the observation that metastatic and nonmetastatic cells
home to target organs with the same efficiency and kinetics supports
the view that adhesion molecules rather control processes after
homing.6-8 The most compelling evidence supporting this view is that mice deficient in intercellular adhesion molecule (ICAM-1)
are resistant to dissemination of lymphoma cells to peripheral organs,
yet lymphoma cells migrate with the same efficiency to target organs in
both normal and ICAM-1-deficient mice.5
Although the resistance mechanism of ICAM-1-deficient mice to lymphoma
metastasis is still unclear, 2 possible scenarios deserve particular
attention. First, it is conceivable that resistance simply consists in
the absence of ICAM-1 induced "tumor welcoming signals" in
stromal cells. Indeed, ICAM-1 is a known transducer of intracellular
signals via their cytoplasmic domains.9-11 Moreover, the
essential role of peritumoral cells in cancer metastasis is now well
accepted, most notably following the results of Masson et
al,12 who recently showed that fibroblasts isolated from stromelysin-3-deficient mice failed to support the growth of human breast cancer cells in nude mice. The second scenario explaining the
resistance of ICAM-1-deficient mice could be that contact of leukocyte
function-associated antigen (LFA-1)-bearing lymphoma cells to ICAM-1
normally up-regulates the expression of specific genes in the tumor
cells, providing them with the ability to grow into tumors in the
target organs. Integrins generally activate, via their cytoplasmic
domains, a number of physiologic processes that provide normal and
transformed cells with the ability to disseminate.13 Thus,
the truncation of the cytoplasmic domain of the Mice
Antibodies
Culture of cell lines The mouse thymic lymphoma lines 164T2 and 374 were developed in vitro from a radiation-induced thymic lymphoma in C57BL/Ka mice, as previously described.5 All cell lines were maintained in culture using RPMI 1640 supplemented with 10% fetal calf serum (FCS), 2 mM glutamine, and 10 mM HEPES buffer (N-2-hydroxyethyl-piperazine-N-2-ethane sulfonic acid).Lymphoid tumor growth in spleen, kidneys, liver, and lymph nodes To induce lymphoma, mice at least 6 to 8 weeks old were injected via the tail vein with 106 lymphoma cells resuspended in 200 µL phosphate-buffered saline (PBS). When clinical signs of lymphoma became evident (dyspnea, runting, and splenomegaly), the animals were killed, and spleen, lungs, ovaries, kidneys, liver, and lymph nodes harvested, weighed, and fixed in 10% formalin for histologic examination.In vivo selection of highly metastatic lymphoma cell lines The aggressive 164T2S11 (S11) and 164T2S19 (S19) cell lines were obtained from serial in vivo passages of the parent 164T2 line in young adult C57BL/6 males using the spleen as the organ from which lymphoma cells were harvested after each passage. Briefly, for each passage, 6- to 8-week-old mice were injected via the tail vein with 106 lymphoma cells. When mice presented clinical signs of lymphoma, they were killed, and lymphoma cells were isolated from the spleen. A leukocyte suspension was obtained by removing red blood cells using the standard ammonium chloride-based protocol. Two clones were finally established after 11 and 19 passages, respectively (S11 and S19). These clones were maintained in culture without loss of aggressiveness.RNA isolation and analysis Total cellular RNA was isolated from lymphoma cells using Trizol reagent (Life Technologies, Mississauga, Canada) according to the manufacturer's instructions. First-strand cDNA was prepared from 3 µg total cellular RNA in a 30-µL reaction volume, using 40 U M-MuLV Reverse Transcriptase (Boehringer Mannheim, Laval, Canada). After reverse transcription, the MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP) cDNA were amplified using specific primers (Table 1). Expression of -actin
(Stratagene, La Jolla, CA) mRNA was monitored as a control using
commercially available primers. TIMP-2-specific primers were carefully
chosen to react with the different mRNA messages possibly resulting
from alternative polyadenylation/termination site usage observed
previously.22 Amplification was conducted using the
polymerase chain reaction (PCR) core kit (Boehringer Mannheim). Thirty
cycles of amplification were performed in a thermal cycler (model
PTC-100TM, MJ Research, Watertown, MA) using the following programmed
step cycle: 94°C for 1 minute, 58°C for 2 minutes, and 72°C
for 3 minutes. Five to 10 µL of the reaction mixture was
size-separated on a 1.5% agarose gel and specifically amplified
products were detected by ethidium bromide staining and UV
transillumination. Semiquantitative analysis was conducted using a
computerized densitometric imager (Model GS-670; Bio-Rad, Mississauga,
Canada).
Zymography Production and secretion of MMP in cell culture supernatants was measured as previously described.23 Briefly, cells were cultured in 24-well plates for 24 hours, in serum-free medium with or without PMA (10 ng/mL). Supernatants (1 mL) were then collected and centrifuged at 1200 rpm for 10 minutes to remove contaminating cells and debris. The supernatants were lyophilized and resuspended in 100 µL Dulbecco's modified Eagle's medium. Aliquots of 20 µL were subjected to electrophoresis on a 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) containing 1 mg/mL denatured collagen (Sigma, St. Louis, MO). After electrophoresis, the gel was washed to remove SDS and incubated in a renaturating buffer (50 mM Tris, 5 mM CaCl2, 0.02% NaN3, 3.1% Triton X-100) for 18 hours at 37°C. The gels were stained with Coomassie brilliant blue and destained in 30% (v/v) methanol/10% (v/v) acetic acid. The proteolytic activity was identified as a clear band on a blue background. Quantitative analysis of activity was conducted using a computerized densitometric imager.Flow cytometric analysis Cells were stained at 4°C and washed with PBS containing 0.5% bovine serum albumin (BSA) and 0.2% sodium azide (PBA). Prior to staining, cells were incubated with 10 µg/mL human IgG (Sigma) for 20 minutes at 4°C to block nonspecific binding. Fluorochrome- or biotin-labeled mAbs were then added at appropriate concentrations and incubated for another 20 minutes. Cells were then washed 4 times with PBA. For indirect staining with streptavidin-PE, cells were washed 3 times following the reaction with the first mAb and then incubated 20 minutes on ice with the fluorescent conjugate. Results shown are representative of at least 3 independent experiments. Flow cytometric analyses were performed on a Coulter XL-MCLTM flow cytometer (Coulter Electronics, Hialeah, FL).In vivo migration assays The ability of lymphoma cells to migrate to target organs was analyzed using standard indium (In) labeling of lymphoma cells, as previously described.7 Briefly, 107 cells were labeled with 10 mCi 111In in 0.5 mL RPMI for 15 minutes at room temperature. The cells were washed 4 times with RPMI containing serum and resuspended in PBS. The viability of labeled cells was over 95% as determined by trypan blue exclusion. Each mouse was injected intravenously with 106 cells (0.5 to 1 × 106 cpm). At 3, 12, and 24 hours, animals (5 mice for each time point) were killed and kidneys, spleen, liver, brain, ovaries, testis, and thymus, as well as heparinized blood samples, were collected. Calculations of the percentage of lymphoma cells per target organs were corrected to take into account the short-half-life of 111In. The total radioactivity in circulating blood was estimated in 400 µL aliquots of blood and assumed a total volume of 2 mL circulating blood per mouse.Statistical analysis Data are presented as means ± SD. Student t test was used to test for statistical significance.
Increased aggressiveness of lymphoma cells induced by serial in vivo passages To determine whether the resistance of ICAM-1-deficient mice could be overcome by increasing the aggressiveness of the lymphoma cells, we generated highly metastatic clones by serial in vivo passages of 164T2 cells in C57BL/6 mice. After 11 such passages, a first clone, 164T2S11 (S11) was obtained and maintained in vitro without loss of aggressiveness. The S11 lymphoma cells induced lymphoid tumors in 99% of injected male or female C57BL/6 mice (Table 2), a significant increase over the parent 164T2 clone (P 0.001), which induced tumors in < 50% of male C57BL/6 mice,5 and rarely (1 of 11) in
females. Furthermore, in both male and female C57BL/6 mice, the
lymphoid tumors induced by S11 developed much more rapidly than those
induced by 164T2 cells (P 0.001). The size and organ
distribution of the lymphoid tumors induced by both cell lines did not
differ significantly (data not shown). Despite the fact that lymphoma
cells were selected from the spleen throughout their in vivo passages,
no changes in organ distribution were observed, because both S11 and
164T2 consistently induced lymphoid tumors in kidneys, spleen, ovaries,
and liver. Thus, in vivo passages increased aggressiveness of 164T2
clone but did not modify target organ distribution. This observation
was consistent with the results of the homing test. We injected
106 111In-labeled cells intravenously to
determine the distribution of the cells in the mouse. The in vivo
selection process did not alter the homing pattern of the lymphoma
cells. Both 164T2 and S11 have identical homing kinetics at 30 minutes,
3 hours, and 24 hours after injection. Both cell lines showed a
transient homing to the lungs before colonizing kidneys, liver, and
spleen. Less than 0.5% of the cells remained in circulation 24 hours
after injection. Similarly, using a panel of 16 antibodies specific for
cell surface molecules normally expressed by T-lymphocyte subsets, we
found that increased aggressiveness did not modify the repertoire of
cell adhesion molecules expressed by the parent cell line (Table
3) nor their expression level (data not
shown).
Increased aggressiveness correlates with increased MMP-9 expression in lymphoma cells Because production of high levels of MMP-9 is a characteristic of aggressive lymphoma cells,16,24 we compared the production of MMP-9 in the parent 164T2 clone and the S11 subclone. We found that S11 cells produced more MMP-9 constitutively, whereas expression of MMP-9 in 164T2 required activation (Figure 1). This increase of MMP-9 expression on passage of the lymphoma cells in vivo was even more noticeable when the 164T2 cells were passaged 19 times. Because tumor growth and metastasis of T-cell lymphoma are inhibited by high-level TIMP-1 production,25 we also measured the level of TIMP-1, TIMP-2, TIMP-3, and TIMP-4 in both cell lines. As in the case of 164T2, we found that in S11 TIMP-1 expression was only detectable on activation with PMA (Figure 2). The expression level of TIMP-1 on activation, however, significantly decreased with increased numbers of in vivo passages. In contrast to TIMP-1, the expression level of TIMP-2 was constitutive in all cell lines but showed variable expression on passages. No expression of TIMP-3 and TIMP-4 were detected (data not shown).
Ability of aggressive lymphoma cells to overcome the resistance of ICAM-1-deficient mice We tested whether the highly aggressive phenotype of S11 allowed these cells to overcome the resistance of ICAM-1-deficient mice. For this purpose, 106 S11 and 164T2 (control) cells were injected intravenously to C57BL/6tm1bay mice. As we previously reported,5 there was no evidence of tumors in any organ of male (0 of 15) and female (0 of 4) ICAM-1-deficient mice injected with the 164T2 cells (Table 4). In contrast, S11 lymphoma cells induced tumors in all male (9 of 9) and almost all female (7 of 8) ICAM-1-deficient mice. The resistance of ICAM-1-deficient mice could also be overcome by the injection of S19 lymphoma cells (data not shown). The distribution pattern of tumors induced by S11 in male ICAM-1-deficient mice was identical to that induced by 164T2 in normal male or female C57BL/6 mice (i.e., spleen, liver, lymph nodes, and kidneys). In female ICAM-1-deficient mice, however, tumors developed first in the ovaries, although histologic examination of these mice showed that lymphoma cells significantly invaded the other organs as well. The homing property of S11 was identical with that of 164T2 in both normal and ICAM-1-deficient mice, as determined by the 111In migration assay (data not shown). Whether this distinct pattern of organ distribution between male and female ICAM-1-deficient mice is due to the repertoire of ICAM-1 isoforms is under investigation.
Ability of LFA-1-negative T lymphoma cells to spread in normal mice The above data suggest that the increased aggressiveness of S11 can overcome the resistance of ICAM-1-deficient mice. However, alternative splicing of the icam-1 gene and the localization of the mutation in ICAM-1-deficient mice leave a basal level of ICAM-1 expression in these mice, and because S11 expresses high levels of LFA-1, which can bind to the residual ICAM-1 isoforms, it was still conceivable that increased aggressiveness alone was not sufficient to produce lymphoma in absence of ICAM-1-mediated signals. In fact, we had no hard evidence to indicate that lymphoma dissemination could occur in absence of LFA-1/ICAM-1-mediated adhesion. To directly address this issue, we have established an independent new lymphoma cell line, 374. Just like the parent 164T2 line, this T-lymphoma cell line (as evidenced by the expression of the TcR ) was also isolated from a
radiation-induced thymic lymphoma and maintained in culture. In
contrast to other T-lymphoma cell lines, however, we found that the 374 cells lacked any detectable expression of LFA-1 on its surface (Figure
3A). The 374 cells produced lymphoma systemically in normal mice when injected intravenously (Table 5). Moreover, just like other aggressive
lymphoma cells, the 374 cells produced high levels of MMP-9
constitutively (Figure 3B). We thus intravenously injected
ICAM-1-deficient mice with 374 and found that these mice developed
tumors despite the absence of LFA-1 on the surface of the tumor cells
(Table 5). The organ distribution pattern induced by 374 cells was
identical in both male and female ICAM-1-deficient mice and showed
tumor development in kidneys, liver, spleen, lungs, and lymph nodes.
The most compelling evidence that intercellular contact via cell adhesion molecules plays a crucial role in the control of lymphoma metastasis is the fact that genetic ablation of the icam-1 gene in mice confers resistance to dissemination of lymphoma following intravenous injection of malignant lymphoma cells.5 In the present work, we have shown: (1) that in vivo passage failed to modify the repertoire of cell adhesion molecules at their surface, nor did it exert a selective pressure that would modify the homing pattern of the lymphoma cells; (2) that a selective pressure favored the emergence of aggressive lymphoma cells that constitutively expressed MMP-9; and (3) that increased aggressiveness overcame the resistance of ICAM-1-deficient mice to lymphoma metastasis. These results are consistent with the idea that intercellular adhesion-dependent post-homing events not only control lymphoma metastasis, but apply a selective pressure that favors the constitutive expression of tumor-specific genes that normally are induced on intercellular contact.
The authors thank Ms Claire Beauchemin and Ms Doris Legault for their excellent technical support.
Submitted May 12, 1999; accepted August 31, 1999.
Supported by the Medical Research Council of Canada and by the Fonds pour la Formation de Chercheur et d'Aide à la Recherche (FCAR).
Reprints: Yves St-Pierre, INRS-Institut Armand-Frappier, 531 Boul. des Prairies Laval, Québec, Canada H7V1B7; e-mail: yves_st-pierre{at}inrs-iaf.uquebec.ca.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
1.
Gosslar U, Jonas P, Luz A, et al.
Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis.
Proc Natl Acad Sci U S A.
1996;93:4821-4826 2. Zahalka MA, Okon E, Gosslar U, Holzmann B, Naor D. Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent. J Immunol. 1995;154:5345-5355[Abstract]. 3. Juliano R. Signal transduction by integrins and its role in the regulation of tumor growth. Cancer Metastasis Rev. 1994;13:25-30[Medline] [Order article via Infotrieve]. 4. Yamamoto H, Irie A, Fukushima Y, et al. Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin alpha6 subunit expression. Int J Cancer. 1996;65:519-524[Medline] [Order article via Infotrieve].
5.
Aoudjit F, Potworowski EF, Springer TA, St-Pierre Y.
Protection from lymphoma metastasis in ICAM-1 mutant mice: a post-homing event.
J Immunol.
1998;161:2333-2338 6. Dolcetti R, Maestro R, Gasparotto D, Rizzo S, Boiocchi M. Adhesion molecule expression does not influence the leukemic behavior of murine T-cell lymphomas. Leukemia. 1992;6:101S-105S.
7.
Aoudjit F, Potworowski EF, St-Pierre Y.
The metastatic characteristics of murine lymphoma cell lines in vivo are manifested after target organ invasion.
Blood.
1998;91:623-629 8. Jonas P, Holzmann B, Jablonski-Westrich D, Hamann A. Dissemination capacity of murine lymphoma cells is not dependent on efficient homing. Int J Cancer. 1998;77:402-407[Medline] [Order article via Infotrieve].
9.
Holland J, Owens T.
Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line. The activation of Lyn tyrosine kinase and the mitogen-activated protein kinase pathway.
J Biol Chem.
1997;272:9108-9112
10.
Etienne S, Adamson P, Greenwood J, Strosberg AD, Cazaubon S, Couraud PO.
ICAM-1 signaling pathways associated with Rho activation in microvascular brain endothelial cells.
J Immunol.
1998;161:5755-5761 11. Sano H, Nakagawa N, Chiba R, Kurasawa K, Saito Y, Iwamoto I. Cross-linking of intercellular adhesion molecule-1 induces interleukin-8 and RANTES production through the activation of MAP kinases in human vascular endothelial cells. Biochem Biophys Res Commun. 1998;250:694-698[Medline] [Order article via Infotrieve].
12.
Masson R, Lefebvre O, Noel A, et al.
In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy.
J Cell Biol.
1998;140:1535-1541 13. Kumar CC. Signaling by integrin receptors. Oncogene. 1998;17:1365-1373[Medline] [Order article via Infotrieve].
14.
Bittner M, Gosslar U, Luz A, Holzmann B.
Sequence motifs in the integrin alpha 4 cytoplasmic tail required for regulation of in vivo expansion of murine lymphoma cells.
J Immunol.
1998;161:5978-5986 15. Aoudjit F, Potworowski EF, St-Pierre Y. Bi-directional induction of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 during T lymphoma/endothelial cell contact: implication of ICAM-1. J Immunol. 1998;160:29672973. 16. Kossakowska AE, Urbanski SJ, Huchcroft SA, Edwards DR. Relationship between the clinical aggressiveness of large cell immunoblastic lymphomas and expression of 92 kDa gelatinase (type IV collagenase) and tissue inhibitor of metalloproteinases-1 (TIMP-1) RNAs. Oncol Res. 1992;4:233-240[Medline] [Order article via Infotrieve].
17.
Sligh JE Jr, Ballantyne CM, Rish SS, et al.
Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1.
Proc Natl Acad Sci U S A.
1993;90:8529-8533 18. Davignon D, Martz E, Reynolds T, Kürzinger K, Springer TA. Monoclonal antibody to a novel function-associated antigen (LFA-1): mechanism of blocking of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981;127:590-595[Medline] [Order article via Infotrieve].
19.
Miyake K, Medina K, Ishara K, Kimoto M, Auerbach R, Kincade PW.
A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture.
J Cell Biol.
1991;114:557-565
20.
Leo O, Foo M, Sachs DH, Samelson LE, Bluestone JA.
Identification of a monoclonal antibody specific for a murine T3 polypeptide.
Proc Natl Acad Sci U S A.
1987;84:1374-1378 21. Takei F. Inhibition of mixed lymphocyte response by a rat monoclonal antibody to a novel murine lymphocyte activation antigen (MALA-2). J Immunol. 1985;134:1403-1407[Abstract].
22.
Hammani K, Blakis A, Morsette D, et al.
Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene.
J Biol Chem.
1996;271:25,498-25,505 23. Aoudjit F, Esteve PO, Desrosiers M, Potworowski EF, St-Pierre Y. Gelatinase B (MMP-9) production and expression by stromal cells in the normal and adult thymus and experimental thymic lymphoma. Int J Cancer. 1997;71:71-78[Medline] [Order article via Infotrieve]. 24. Okada T, Li J, Kodaka M, Okuno H. Enhancement of type IV collagenases by highly metastatic variants of HT1080 fibrosarcoma cells established by a transendothelial invasion system in vitro. Clin Exp Metastasis. 1998;16:267-274[Medline] [Order article via Infotrieve].
25.
Kruger A, Fata JE, Khokha R.
Altered tumor growth and metastasis of a T-cell lymphoma in Timp-1 transgenic mice.
Blood
1997;90:1993-2000 26. Aoudjit F, Masure S, Opdenakker G, Potworowski EF, St-Pierre Y. Gelatinase B (MMP-9) but not its inhibitor (TIMP-1) dictates the growth rate of experimental thymic lymphoma. Int J Cancer. 1999;82:743-747[Medline] [Order article via Infotrieve]. 27. Tang DG, Honn KV. Adhesion molecules and tumor metastasis: an update. Invasion Metastasis. 1994;14:109-122[Medline] [Order article via Infotrieve]. 28. Huang YW, Baluna R, Vitetta ES. Adhesion molecules as targets for cancer therapy. Histol Histopathol. 1997;2:467-477. 29. St-Pierre Y, Aoudjit F, Lalancette M, Potworowski EF. Dissemination of T cell lymphoma to target organs: a post-homing event implicating ICAM-1 and matrix metalloproteinases. Leuk Lymphoma. 1999;34:53-61[Medline] [Order article via Infotrieve].
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
 |
|
  M. Demers, K. Biron-Pain, J. Hebert, A. Lamarre, T. Magnaldo, and Y. St-Pierre Galectin-7 in Lymphoma: Elevated Expression in Human Lymphoid Malignancies and Decreased Lymphoma Dissemination by Antisense Strategies in Experimental Model Cancer Res., March 15, 2007; 67(6): 2824 - 2829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Demers, T. Magnaldo, and Y. St-Pierre A Novel Function for Galectin-7: Promoting Tumorigenesis by Up-regulating MMP-9 Gene Expression Cancer Res., June 15, 2005; 65(12): 5205 - 5210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Belanger and Y. St-Pierre Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: implication of L-selectin in the growth of thymic lymphoma Blood, June 15, 2005; 105(12): 4800 - 4806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rosette, R. B. Roth, P. Oeth, A. Braun, S. Kammerer, J. Ekblom, and M. F. Denissenko Role of ICAM1 in invasion of human breast cancer cells Carcinogenesis, May 1, 2005; 26(5): 943 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. De Noncourt, O. Robledo, T. Alain, A. E. Kossakowska, S. J. Urbanski, E. F. Potworowski, and Y. St-Pierre Leukocyte elastase in murine and human non-Hodgkin lymphomas J. Leukoc. Biol., October 1, 2001; 70(4): 585 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Koivunen, T.-M. Ranta, A. Annila, S. Taube, A. Uppala, M. Jokinen, G. van Willigen, E. Ihanus, and C. G. Gahmberg Inhibition of {beta}2Integrin-Mediated Leukocyte Cell Adhesion by Leucine-Leucine-Glycine Motif-Containing Peptides J. Cell Biol., May 28, 2001; 153(5): 905 - 916. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2000 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Top
Abstract
Introduction
4
chain),
chain),
) or presence
(+) of 50 nM PMA for 12 hours. Supernatants were collected,
lyophilized, and assayed for their gelatinase content by zymography.
Results are representative of at least 3 independent experiments.
