Increased Osteopontin‐Positive Macrophage Expression in Colorectal Cancer Stroma with Synchronous Liver Metastasis

Abstract

The macrophages that infiltrate the tumor stroma are termed tumor-associated macrophages (TAMs). TAMs contribute to hematogenous spread of cancer cells especially liver metastasis. Osteopontin (OPN) is also related to tumor metastasis and proliferation of tumors. OPN is mainly expressed in macrophages of stroma other than that of tumor cells. The aim of the present study was to investigate differences in OPN-positive TAMs between cases of colorectal cancer with synchronous liver metastasis and those without liver metastasis. A total of 54 subjects who had undergone resection of a primary tumor of advanced colorectal cancer were classified into two groups: synchronous colorectal liver metastasis group (s-CLM group; n = 30) and no liver metastasis group (controls; n = 24). The number of OPN- and CD68-positive cells and the microvascular density (MVD) were determined using the CD105 antibody in the stroma of the invasive margin of the tumor and in the stroma of the central area. There was no difference in the patient profiles between the two groups. OPN and MVD expression in the central area were significantly higher in the s-CLM group (OPN: control 4.3 +/- 1.42, s-CML 12.1 +/- 1.42, P < 0.05; MVD: control 18.5 +/- 2.86, s-CML 27.5 +/- 2.94, P < 0.05), whereas CD68 expression in the invasive margin was significantly higher in the control group (control 98.9 +/- 7.31, s-CML 29.0 +/- 4.44, P < 0.05). These data suggest that OPN in the central area may have induced high microvascular density, which led to liver metastasis. Thus, OPN might be a potential target for novel antiangiogenesis therapy for treating colorectal cancer.