PT  - JOURNAL ARTICLE
AU  - Sehgal, Inder
AU  - Baley, Patricia A.
AU  - Thompson, Timothy C.
TI  - Transforming Growth Factor β1 Stimulates Contrasting Responses in Metastatic <em>versus</em> Primary Mouse Prostate Cancer-derived Cell Lines <em>in Vitro</em>
DP  - 1996 Jul 15
TA  - Cancer Research
PG  - 3359--3365
VI  - 56
IP  - 14
4099  - http://cancerres.aacrjournals.org/content/56/14/3359.short
4100  - http://cancerres.aacrjournals.org/content/56/14/3359.full
SO  - Cancer Res1996 Jul 15; 56
AB  - Tumor progression to the stage of metastasis may result in part from the selection of certain primary tumor cell clones which are phenotypically competent for survival, invasion, and growth at secondary sites. Selection for traits such as loss of growth inhibitory responses, acquisition of increased adhesiveness, increased local immunosuppression, and enhanced motility and collagenase activities likely contribute to cancer progression and may be regulated through the action of growth factors. The transforming growth factor β (TGF-β) family of growth factors has often been associated with these traits and tumor progression; therefore, elimination or subversion of TGF-β-responsive pathways should be considered as a mechanistic framework for metastatic events. In this report, we have compared growth and extracellular matrix responses to TGF-β in six metastatic and six primary tumor-derived cell lines in a mouse model of prostate cancer. We have found that tumor cell lines derived from focal pulmonary metastasis secreted relatively greater quantities of total TGF-βs, lost most or all TGF-β1 growth inhibition, but responded to TGF-β1 through induction of the type IV collagenase matrix metalloproteinase-9, whereas cell lines derived from tumors which proliferated at the primary site retained the growth inhibition but lacked collagenase activity. Synthesis of another extracellular matrix protein, plasminogen activator inhibitor 1, was stimulated by TGF-β1 in both primary as well as metastatic tumors. These results suggest that acquisition of differential responses to the TGF-β family could results in phenotypic traits which facilitate tumor metastasis from certain primary site clones. ©1996 American Association for Cancer Research.