Basal cell adhesion molecule (BCAM) promotes mesothelial-to-mesenchymal transition and tumor angiogenesis through paracrine signaling
Cell Communication and Signaling, 2025
Sivakumar S., Lieber S., Dietze R., Beutgen V., Sutor E., Heidemann S., Finkernagel F., Teply-Szymanski J., Nist A., Stiewe T., Roth K., Reinartz S., Graumann J., Müller-Brüsselbach S., Müller R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Pathophysiology | Cell Culture Supernatant |  Olink Explore 3072/384 |
Abstract
Background
High expression of basal cell adhesion molecule (BCAM) is a hallmark of ovarian cancer (OC) progression. BCAM facilitates transcoelomic dissemination by promoting mesothelial cell clearance at peritoneal attachment sites of tumor cell spheroids. We investigated how BCAM mediates this effect and potentially drives other pro-metastatic functions.
Methods
The impact of BCAM on the tumor cell secretome and the mesothelial cell phenotype was analyzed by affinity proteomics, bulk and single-cell RNA sequencing, life-cell and multiphoton microscopy, biochemical and functional in vitro assays as well as a murine tumor model. BCAM manipulation involved ectopic overexpression, inducible expression and treatment with soluble BCAM.
Results
All forms of BCAM enhanced the secretion of cytokines that impact cell motility, mesenchymal differentiation and angiogenesis, including AREG, CXCL family members, FGF2, TGFB2, and VEGF. Notably, their levels in OC ascites were correlated with BCAM expression, and recombinant BCAM-induced cytokines triggered mesothelial-mesenchymal transition (MMT). Mesothelial cells undergoing MMT exhibited enhanced motility away from attaching tumor spheroids, leading to mesothelial clearance at spheroid attachment sites. BCAM-mediated MMT-associated transcriptional changes were also observed in subpopulations of omental mesothelial cells from OC patients, and were associated with poor survival. Consistent with the secretome data, BCAM induced endothelial tube formation in vitro and markedly promoted tumor angiogenesis in a mouse model.
Conclusion
We have identified previously unknown functions of the BCAM-induced secretome potentially impacting distinct stages of OC metastasis. While BCAM’s impact on MMT may facilitate initiation of micrometastases, neo-angiogenesis is essential for tumor growth. Taken together with the observed clinical adverse association, our findings underscore the potential of BCAM as a therapeutic target.