Fibroblast heterogeneity and metastases in breast cancer
It's well known that cancer associated fibroblasts (CAFs) are involved with numerous tumor processes including angiogenesis, proliferation of tumor cells, treatment resistance, immunomodulation and the formation of metastases. In particular, CAFs are known to increase tumor invasion and the formation of metastases in breast cancer. However, if the role of CAFs in tumor invasion is well established the role they play in metastases and lymph nodes hasn't been studied to such an extent.
In this article, Fatima Mechta-Grigoriou's team study the impact of CAF subtypes on metastatic dissemination by analyzing their heterogeneity in tumor cell invaded lymph nodes and their involvement in the spread of cancer cells.
The team show that 2 CAF subtypes (CAF-S1 and CAF-S4) accumulate significantly in the lymph nodes and postively modulate the invasion of cancer cells via complementary mechanisms. CAF-S1 induces the migration of cancer cells and the initiation of a epithelio-mesenchymal transition (via the secretion of CXCL12/TGFβ) while the contractile properties of CAF S4 induce the motility of cancer cells and their invasion in 3 dimensions (via a NOTCH mediated signaling channel).
Importantly, this study shows that CAF-S1 and CAF-S4 content in the lymph nodes at diagnosis is a prognostic factor. Patients with high levels of CAF-S4 are, in fact, more likely to develop distant metastases in the long term and deserve to have regular clinical monitoring.