sb-290157 and Lung-Neoplasms

Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown.. We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer.. C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models.. C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.

Topics: Animals; Arginine; Benzhydryl Compounds; Breast Neoplasms; Cancer-Associated Fibroblasts; Cell Line, Tumor; Complement C3; Cytokines; Extracellular Matrix Proteins; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mice; Neoplasm Invasiveness; Neoplasm Transplantation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, Complement; Signal Transduction