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CD14-expressing bladder cancer cells establish tumor-promoting inflammation and drive tumor cell proliferation [electronic resource]

Keratin 14 (KRT14) expression marks the most primitive differentiation state in bladder cancer (BC) cells. However, the mechanisms by which KRT14-expressing cells promote tumorigenicity remain undefined. We found that KRT14-expressing cells express higher levels of CD14 and inflammatory factors such as IL6 and IL8. Using a syngeneic mouse BC model, we isolated CD14 high BC cells and show that this population is more tumorigenic compared to CD14 low cells and forms tumors that are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14 high BC cells directly drive the recruitment and polarization of monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14 low BC cells have higher relative proliferation, which is markedly increased when stimulated by factors produced by CD14 high cells. Collectively, we demonstrate that CD14 high BC cells orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.