title: Thrombospondin-1 and pigment epithelium-derived factor enhance responsiveness of KM12 colon tumor to metronomic cyclophosphamide but have disparate effects on tumor metastasis.
abstract: The anti-tumor activity, metronomic chemotherapy sensitization potential and metastatic effects of the endogenous angiogenesis inhibitors thrombospondin-1 and PEDF were investigated in KM12 colon adenocarcinoma xenografts. Thrombospondin-1 and PEDF decreased KM12 tumor microvessel density, increased macrophage infiltration, and improved responsiveness to metronomic cyclophosphamide (CPA) treatment, but did not activate the anti-tumor innate immunity that metronomic CPA induces in other tumor models. Moreover, thrombospondin-1, but not PEDF, significantly increased KM12 metastasis to the lung, while PEDF augmented the anti-metastatic activity of metronomic CPA. Thus, while thrombospondin-1 and PEDF both increase the KM12 tumor responsiveness to metronomic CPA, they have disparate effects on tumor metastasis.
authors.affiliation: Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, MA 02215, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.forename: David J
authors.initials: DJ
authors.lastname: Waxman
mesh_terms: D059250:Administration, Metronomic; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D005136:Eye Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000032:analysis / Q000502:physiology*; D015843:Serpins / Q000032:analysis / Q000502:physiology*; D019700:Thrombospondin 1 / Q000032:analysis / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D019700:Thrombospondin 1; D000099174:Pigment Epithelium-Derived Factor