Scatter factor promotes motility of human glioma and neuromicrovascular endothelial cells

Katrin Lamszus, Nils Ole Schmidt, Liang Jin, John Laterra, David Zagzag, Dennis Way, Marlys H Witte, Martin E Weinand, Itzhak D. Goldberg, Manfred Westphal, Eliot M. Rosen

Research output: Contribution to journalArticle

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Abstract

Malignant gliomas are characterized by rapid growth, infiltration of normal brain tissue, and high levels of tumor-associated angiogenesis. The genetic and local environmental tissue factors responsible for the malignant progression from low to high grade gliomas and the highly malignant behavior of glioblastomas are not well understood. In a study of 77 human brain tissue extracts, high grade (III-IV) tumors had significantly greater scatter factor (SF) content than did low grade tumors or non-neoplastic tissue. To investigate the potential significance of SF accumulation in gliomas, we measured the effects of SF on DNA synthesis and motility of cultured human glioma cell lines. SF stimulated DNA synthesis in 7110 glioma cell lines and in 3/3 neuromicrovascular endothelial cell (NMVEC) lines, consistent with our previous report that SF stimulated cell proliferation of a few human glioma cell lines. SF markedly stimulated the chemotactic migration of 10/10 glioma cell lines as well as 3/3 NMVEC lines. In addition, SF stimulated the 2- dimensional migration of glioma cells on culture surfaces coated with specific extracellular matrix molecules (collagen IV, laminin, and fibronection). As expected based on these biologic responses to SF, 10/10 glioma lines and 4/4 NMVEC lines expressed mRNA for c-met, the SF receptor. To assess the possible in vivo significance of these migration assays, we compared the chemotactic response of a glioma cell line to human brain cyst fluids and tumor extracts that contained high or low SF concentrations. Fluids and extracts with high SF content tended to induce higher levels of chemotactic migration than did fluids and extracts with low SF content. Addition of anti-SF monoclonal antibody (MAb) inhibited migration induced by fluids and extracts with high SF content by about 30-50%.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalInternational Journal of Cancer
Volume75
Issue number1
DOIs
StatePublished - Jan 5 1998

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Hepatocyte Growth Factor
Glioma
Endothelial Cells
Cell Line
Neoplasms
Brain
Proto-Oncogene Proteins c-met
Cyst Fluid
Tissue Extracts
DNA
Thromboplastin
Laminin
Glioblastoma
Extracellular Matrix
Collagen
Cell Culture Techniques
Monoclonal Antibodies
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Scatter factor promotes motility of human glioma and neuromicrovascular endothelial cells. / Lamszus, Katrin; Schmidt, Nils Ole; Jin, Liang; Laterra, John; Zagzag, David; Way, Dennis; Witte, Marlys H; Weinand, Martin E; Goldberg, Itzhak D.; Westphal, Manfred; Rosen, Eliot M.

In: International Journal of Cancer, Vol. 75, No. 1, 05.01.1998, p. 19-28.

Research output: Contribution to journalArticle

Lamszus, Katrin ; Schmidt, Nils Ole ; Jin, Liang ; Laterra, John ; Zagzag, David ; Way, Dennis ; Witte, Marlys H ; Weinand, Martin E ; Goldberg, Itzhak D. ; Westphal, Manfred ; Rosen, Eliot M. / Scatter factor promotes motility of human glioma and neuromicrovascular endothelial cells. In: International Journal of Cancer. 1998 ; Vol. 75, No. 1. pp. 19-28.
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AU - Lamszus, Katrin

AU - Schmidt, Nils Ole

AU - Jin, Liang

AU - Laterra, John

AU - Zagzag, David

AU - Way, Dennis

AU - Witte, Marlys H

AU - Weinand, Martin E

AU - Goldberg, Itzhak D.

AU - Westphal, Manfred

AU - Rosen, Eliot M.

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AB - Malignant gliomas are characterized by rapid growth, infiltration of normal brain tissue, and high levels of tumor-associated angiogenesis. The genetic and local environmental tissue factors responsible for the malignant progression from low to high grade gliomas and the highly malignant behavior of glioblastomas are not well understood. In a study of 77 human brain tissue extracts, high grade (III-IV) tumors had significantly greater scatter factor (SF) content than did low grade tumors or non-neoplastic tissue. To investigate the potential significance of SF accumulation in gliomas, we measured the effects of SF on DNA synthesis and motility of cultured human glioma cell lines. SF stimulated DNA synthesis in 7110 glioma cell lines and in 3/3 neuromicrovascular endothelial cell (NMVEC) lines, consistent with our previous report that SF stimulated cell proliferation of a few human glioma cell lines. SF markedly stimulated the chemotactic migration of 10/10 glioma cell lines as well as 3/3 NMVEC lines. In addition, SF stimulated the 2- dimensional migration of glioma cells on culture surfaces coated with specific extracellular matrix molecules (collagen IV, laminin, and fibronection). As expected based on these biologic responses to SF, 10/10 glioma lines and 4/4 NMVEC lines expressed mRNA for c-met, the SF receptor. To assess the possible in vivo significance of these migration assays, we compared the chemotactic response of a glioma cell line to human brain cyst fluids and tumor extracts that contained high or low SF concentrations. Fluids and extracts with high SF content tended to induce higher levels of chemotactic migration than did fluids and extracts with low SF content. Addition of anti-SF monoclonal antibody (MAb) inhibited migration induced by fluids and extracts with high SF content by about 30-50%.

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