Malignant transformation of NIH-3T3 cells after subcutaneous co-injection with a reconstituted basement membrane (matrigel).
NIH-3T3 cells are non-tumorigenic when injected into athymic mice. If these cells are mixed with an extract of basement-membrane proteins (matrigel) and injected s.c., they form locally invasive and highly vascularized tumors. Cells cultured from the NIH-3T3-matrigel-induced tumors showed a transformed phenotype and lacked contact inhibition. When cultured in a gel of matrigel, they proliferated and formed branched and invasive colonies. In contrast, the parental NIH-3T3 cells cultured on matrigel remained as cell aggregates and were not invasive. I.V. injections of the tumor-derived NIH-3T3 cells produced many colonies on the surface of the lungs, whereas the parental NIH-3T3 cells were not metastatic. Zymographic analysis of the conditioned media obtained from both the tumor-derived and parental NIH-3T3 cells demonstrated higher amounts of the 72-kDa gelatinase (type-IV collagenase) enzyme in the tumor-derived cells. Also, tumor-derived NIH-3T3 cells, but not parental NIH-3T3 cells, secreted the 92-kDa type-IV collagenase. These studies suggest that the interaction of pre-malignant NIH-3T3 cells with extracellular matrix components may contribute to the process of tumor progression.
Fridman
R
R
Molecular Oncology Inc., Gaithersburg, MD 20878.
Sweeney
T M
TM
Zain
M
M
Martin
G R
GR
Kleinman
H K
HK
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008819:Mice, Nude; D003012:Microbial Collagenase / Q000378:metabolism; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9