Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.

ABSTRACT: The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs. Direct exposure of CAFs to apoptotic 344SQ cells (ApoSQ) inhibited CAF migration and invasion and the expression of CAF activation markers. Enhanced secretion of Wnt-induced signaling protein 1 (WISP-1) by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects. Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP

SUBMITTER: Kim HJ 

PROVIDER: S-EPMC9708692 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature