Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts.
To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1, and collagen type I. Beta1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed fibroblasts.
Brakebusch
C
C
Department of Experimental Pathology, Lund University Hospital, Sweden.
Wennerberg
K
K
Krell
H W
HW
Weidle
U H
UH
Sallmyr
A
A
Johansson
S
S
Fässler
R
R
D000483:Alleles; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D018390:Gene Targeting; D016259:Genes, myc; D011905:Genes, ras; D019012:Integrin beta1 / Q000502:physiology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D014162:Transfection
D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D009363:Neoplasm Proteins