| First Author | Li X | Year | 2021 |
| Journal | Cancer Lett | Volume | 503 |
| Pages | 32-42 | PubMed ID | 33482262 |
| Mgi Jnum | J:303857 | Mgi Id | MGI:6511863 |
| Doi | 10.1016/j.canlet.2021.01.013 | Citation | Li X, et al. (2021) Targeting FAPalpha-expressing tumor-associated mesenchymal stromal cells inhibits triple-negative breast cancer pulmonary metastasis. Cancer Lett 503:32-42 |
| abstractText | Tumor metastasis is the main cause of death in patients with triple-negative breast cancer (TNBC). Bone marrow-derived mesenchymal stem cells (BM-MSCs) have tropism towards tumor tissues, and can be converted into tumor-associated mesenchymal stromal cells (TA-MSCs) to facilitate TNBC metastasis through interactions with tumor-associated macrophages (TAMs). However, the underlying molecular mechanisms are complex and unclear, and effective strategies to suppress tumor metastasis via eliminating TA-MSCs are still lacking. Here, we demonstrate that fibroblast activation protein alpha (FAPalpha) was overexpressed in TA-MSCs, which prompts TA-MSCs to secrete multiple C-C motif chemokine ligands, promoting C-C motif chemokine receptor 2 (CCR2)(+) TAM recruitment and facilitating TAM polarization into the M2 phenotype, thereby promoting TNBC pulmonary metastasis. Z-GP-DAVLBH, an FAPalpha-activated vinblastine prodrug, induces FAPalpha(+) TA-MSC apoptosis, which significantly suppresses CCR2(+) TAM recruitment and polarization, thus inhibiting pulmonary metastasis of orthotopic TNBC cell-derived xenografts and patient-derived xenografts. This study provides insight into an important role of FAPalpha in mediating TA-MSC-induced TNBC metastasis and provides compelling evidence that targeting TA-MSCs with an FAPalpha-activated prodrug is a promising strategy for suppressing TNBC metastasis. |
