title: Chromogranin A regulates tumor self-seeding and dissemination.
abstract: Cancer progression involves the seeding of malignant cells in circulation and the colonization of distant organs. However, circulating neoplastic cells can also reinfiltrate the tumor of origin. This process, called "tumor-self seeding," can select more aggressive cells that may contribute to cancer progression. Here, using mouse mammary adenocarcinoma models, we observed that both tumor self-seeding and organ colonization were inhibited by chromogranin A (CgA), a protein present in variable amounts in the blood of cancer patients. Mechanism studies showed that CgA inhibited the shedding of cancer cells in circulation from primary tumors, as well as the reinfiltration of tumors and the colonization of lungs by circulating tumor cells. CgA reduced gap formation induced by tumor cell-derived factors in endothelial cells, decreased vascular leakage in tumors, and inhibited the transendothelial migration of cancer cells. Together, our findings point to a role for circulating CgA in the regulation of tumor cell trafficking from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the multidirectional trafficking of cancer cells in normal and neoplastic tissues may represent a novel strategy to reduce cancer progression.
authors.affiliation: Division of Molecular Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dondossola
authors.forename: Luca
authors.initials: L
authors.lastname: Crippa
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrero
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D008546:Melanoma, Experimental / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009366:Neoplasm Seeding; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D053379:Chromogranin A; D011994:Recombinant Proteins