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Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines
Author(s) -
Zabrenetzky Vivian,
Harris Curtis C.,
Steeg Patricia S.,
Roberts David D.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590209
Subject(s) - cell culture , cancer research , breast carcinoma , thrombospondin 1 , transfection , thrombospondin , extracellular matrix , tumor progression , carcinogenesis , biology , metastasis , melanoma , pathology , medicine , cancer , breast cancer , angiogenesis , microbiology and biotechnology , metalloproteinase , genetics , matrix metalloproteinase
Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady‐state Thbs‐1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K‐1735 melanoma cell lines of low metastatic potential, including K‐1735 lines transfected with the murine nm23 ‐1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v‐Ki‐ ras , v‐Ha‐ ras or n‐ ras transfectants, which in turn expressed higher TSP levels than tumor‐derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs‐1 steady‐state mRNA levels were greater in the 2 nonmetastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23 ‐1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression.