adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration缺脂联素通过减少巨噬细胞渗透促进小鼠肿瘤的生长.pdfVIP

Adiponectin Deficiency Promotes Tumor Growth in Mice by Reducing Macrophage Infiltration Yutong Sun, Harvey F. Lodish* Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America Abstract Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of both tumors. Immunohistochemical analyses indicated that adiponectin deficiency reduced macrophage recruitment to the tumor, but did not affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In addition, treatment with recombinant adiponectin did not affect the proliferation of cultured B16F10 tumor cells. Importantly, the restoration of microphage infiltration at an early stage of tumorigenesis by means of co-injection of B16F10 cells and macrophages reversed the increased tumor growth in adiponectin knockout mice. Thus, we conclude that the enhanced tumor growth observed in adiponectin deficient mice is likely due to the reduction of macrophage infiltration rather than enhanced angiogenesis. Citation: Sun Y, Lodish HF (2010) Adiponectin Deficiency Promotes Tumor Growth in Mice by Reducing Macrophage Infiltration. PLoS ONE 5(8): e11987. doi:10.1371/journal.pone.0011987 Editor: Samithamby Jeyaseelan, Louisiana State University, United States of America Received May 27, 2010; Accepted July 11, 2010; Published August 5, 2010 Copyright: 2010 Sun,