Background: Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors. Methods: To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages. Results:The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204positive macrophages and a poor outcome (p ϭ 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/ monocyte marker, were of marginal prognostic significance (p ϭ 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages (p ϭ 0.031 and p ϭ 0.031, respectively). Conclusion: These findings demonstrated that CD204-positive macrophages clearly reflect the tumor-promoting phenotype of tumorassociated macrophages in lung adenocarcinoma.

Purpose: Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer.Experimental Design: We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells.Results: Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells.Conclusions: Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer. Clin Cancer Res; 16(1); 121-9. ©2010 AACR.Bone has long been recognized as the most common target organ for prostate cancer metastasis (1, 2). Bone metastasis causes skeletal complications and results in poor prostate cancer outcome in patients (3). Unfortunately, the efficacy of conventional therapies, including androgen deprivation, for the bone metastasis is limited. Despite extensive efforts to develop new therapeutic approach, more efficient treatment of bone metastases from prostate cancer has not been established.Although the precise reason why prostate cancer cells prefer bone tissue is not fully understood, one hypothesis is that the bone is a source of abundant growth factors required for the growth and survival of prostate cancer cells (4). Previously, we established a bone-specific metastasis model of human prostate cancer to investigate the mechanism of bone metastasis from prostate cancer (5). Using this model, in which human adult bones (HAB) were engrafted in mice, we showed previously that the release of growth factors, such as insulin-like growth factors (IGF), arising from bone resorption induced by the tumor cells was important for bone metastasis from prostate cancer (6, 7).IGFs are the most abundant growth factors stored in bone matrix (8). The actions of IGFs are inhibited when they bind to IGF-binding proteins. Prostate cancer cells are known to secrete certa...