Gain or loss of TGFβ signaling in mammary carcinoma cells can promote metastasis

The transforming growth factor beta (TGF beta) is a potent regulator of tumor initiation, progression and metastasis. It has been known for many years that TGF beta signaling in the carcinoma cell can suppress or promote tumor progression depending on the context of stimulation. While the impact of TGF beta 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 beta signaling in carcinoma cells can promote metastasis through carcinoma cell derived TGF beta dependent host-tumor cell interactions in vivo. Further, gain or complete abrogation of TGF beta signaling was shown to result in gene expression signatures that correlated with poor patient prognosis in breast cancer. Specifically, the TGF beta responsive gene expression signature correlated with poor prognosis for estrogen receptor negative (ER(-)) breast cancer while complete abrogation of TGF beta 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 beta dependent host-tumor cell interactions should be considered when designing therapeutic strategies to manage carcinoma progression.