title: Inhibition of macrophage polarization prohibits growth of human osteosarcoma.
abstract: Osteosarcoma is the most malignant bone tumor characterized by high local aggressiveness and poor therapeutic outcome. Tumor-associated macrophages (TAM) have been shown to participate in the development and progress of many types of cancer cells. However, whether TAM may play a role in the pathogenesis of osteosarcoma is largely unknown. In a mouse model of human osteosarcoma implantation, we showed that the recruited macrophages at the site of the implanted tumor were polarized to an M2 subtype (same as TAM) during the development and growth of the osteosarcoma. In a loss-of-function experiment, we deleted these TAM with a specific macrophage-eliminating liposome, which resulted in decreased tumor growth. Moreover, when the epidermal growth factor receptor (EGFR) in the implanted cancer cells was inhibited by shRNA, the tumor failed to grow in response to the recruited macrophages. Taken together, for the first time, we show that the growth of an osteosarcoma is EGFR signaling-dependent and TAM-mediated. Our data suggest that TAM and EGFR may be good targets for treating human osteosarcoma.
authors.affiliation: The Department of Hand and Foot Surgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Guta District, Jinzhou, 121001, China, qiang_xiao14@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.forename: Xuepu
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D012516:Osteosarcoma / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D066246:ErbB Receptors