HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

I. S. Weimar, K. Weijer, P. C M Van Den Berk, E. J. Muller, N. Miranda, A. Q. Bakker, M. H M Heemskerk, A. Hekman, G. C. De Gast, W. R. Gerritsen

Research output: Contribution to journalArticle

Abstract

The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF-c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF-c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalBritish Journal of Cancer
Volume81
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-met
Hepatocyte Growth Factor
SCID Mice
B-Cell Lymphoma
Lymphoma

Keywords

  • c-MET
  • Dissemination
  • HGF/SF
  • Human B-lymphoma cells
  • Retroviral transduction
  • SCID mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Weimar, I. S., Weijer, K., Van Den Berk, P. C. M., Muller, E. J., Miranda, N., Bakker, A. Q., ... Gerritsen, W. R. (1999). HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice. British Journal of Cancer, 81(1), 43-53. https://doi.org/10.1038/sj.bjc.6690649

HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice. / Weimar, I. S.; Weijer, K.; Van Den Berk, P. C M; Muller, E. J.; Miranda, N.; Bakker, A. Q.; Heemskerk, M. H M; Hekman, A.; De Gast, G. C.; Gerritsen, W. R.

In: British Journal of Cancer, Vol. 81, No. 1, 1999, p. 43-53.

Research output: Contribution to journalArticle

Weimar, IS, Weijer, K, Van Den Berk, PCM, Muller, EJ, Miranda, N, Bakker, AQ, Heemskerk, MHM, Hekman, A, De Gast, GC & Gerritsen, WR 1999, 'HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice', British Journal of Cancer, vol. 81, no. 1, pp. 43-53. https://doi.org/10.1038/sj.bjc.6690649
Weimar, I. S. ; Weijer, K. ; Van Den Berk, P. C M ; Muller, E. J. ; Miranda, N. ; Bakker, A. Q. ; Heemskerk, M. H M ; Hekman, A. ; De Gast, G. C. ; Gerritsen, W. R. / HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice. In: British Journal of Cancer. 1999 ; Vol. 81, No. 1. pp. 43-53.
@article{7d7c339ffba74d31a9c1c9c9e8866f64,
title = "HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice",
abstract = "The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF-c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF-c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells.",
keywords = "c-MET, Dissemination, HGF/SF, Human B-lymphoma cells, Retroviral transduction, SCID mice",
author = "Weimar, {I. S.} and K. Weijer and {Van Den Berk}, {P. C M} and Muller, {E. J.} and N. Miranda and Bakker, {A. Q.} and Heemskerk, {M. H M} and A. Hekman and {De Gast}, {G. C.} and Gerritsen, {W. R.}",
year = "1999",
doi = "10.1038/sj.bjc.6690649",
language = "English (US)",
volume = "81",
pages = "43--53",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - HCF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

AU - Weimar, I. S.

AU - Weijer, K.

AU - Van Den Berk, P. C M

AU - Muller, E. J.

AU - Miranda, N.

AU - Bakker, A. Q.

AU - Heemskerk, M. H M

AU - Hekman, A.

AU - De Gast, G. C.

AU - Gerritsen, W. R.

PY - 1999

Y1 - 1999

N2 - The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF-c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF-c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells.

AB - The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF-c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF-c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells.

KW - c-MET

KW - Dissemination

KW - HGF/SF

KW - Human B-lymphoma cells

KW - Retroviral transduction

KW - SCID mice

UR - http://www.scopus.com/inward/record.url?scp=0032588295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032588295&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6690649

DO - 10.1038/sj.bjc.6690649

M3 - Article

C2 - 10487611

AN - SCOPUS:0032588295

VL - 81

SP - 43

EP - 53

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -