Gain or loss of TGF-β signaling in mammary carcinoma cells can promote metastasis

The transforming growth factor beta (TGF-β) is a potent regulator of tumor initiation, progression and metastasis. It has been known for many years that TGF-β signaling in the carcinoma cell can suppress or promote tumor progression depending on the context of stimulation. While the impact of TGF-β on the carcinoma cell is significant, it is now generally accepted that primary and metastatic carcinoma progression is regulated by an intricate network of host-tumor cell interactions. Interestingly, recent results have revealed that gain or loss of TGF-β signaling in carcinoma cells can promote metastasis through carcinoma cell derived TGF-β dependent host-tumor cell interactions in vivo. Further, gain or complete abrogation of TGF-β signaling was shown to result in gene expression signatures that correlated with poor patient prognosis in breast cancer. Specifically, the TGF-β responsive gene expression signature correlated with poor prognosis for estrogen receptor negative (ER-) breast cancer while complete abrogation of TGF-β signaling resulted in a correlation with poor outcome in lymph node positive (LN+) and ER+ breast cancers. Importantly, in both cases the correlation with poor prognosis was linked to carcinoma cell derived interactions with the adjacent microenvironment. Together the current results suggest that, in addition to intrinsic carcinoma cell signaling, TGF-β dependent host-tumor cell interactions should be considered when designing therapeutic strategies to manage carcinoma progression.