Osteopontin expression and distribution in human carcinomas.
Osteopontin expression and distribution in human carcinomas.
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发表时间：
1994-09
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通讯作者：
L. Brown;A. Papadopoulos-Sergiou;B. Berse;E. Manseau;K. Tognazzi;C. Perruzzi;H. Dvorak;D. Senger
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作者：
L. Brown;A. Papadopoulos-Sergiou;B. Berse;E. Manseau;K. Tognazzi;C. Perruzzi;H. Dvorak;D. Senger
骨桥蛋白 (OPN) 是一种分泌型粘附糖蛋白，在多种恶性肿瘤实验模型中显着过度表达。此外，在转移性癌患者的血液中检测到 OPN 水平升高。为了直接研究 OPN 在人类癌症中的表达和分布，我们通过 Northern 分析、原位杂交和免疫组织化学研究了多种常见肿瘤。 Northern 分析研究的所有 14 个肿瘤均显示，与相应的正常组织相比，OPN 信使 (m)RNA 显着增加。此外，通过原位杂交研究的 76 种癌症中，有 71 种检测到 OPN mRNA 的强烈标记。在大多数研究的癌症（结肠癌、胃癌、十二指肠癌、胰腺癌、乳腺癌、肺癌、膀胱癌、前列腺癌、卵巢癌、甲状腺癌和黑色素瘤）中，肿瘤细胞未检测到 OPN mRNA 标记；然而，巨噬细胞与肿瘤细胞密切相关，OPN 转录物被强烈标记。在肾癌和子宫内膜癌中，肿瘤细胞和宿主巨噬细胞都强烈标记 OPN mRNA。巨噬细胞中 OPN mRNA 的存在在肿瘤边缘（即肿瘤/基质界面）和肿瘤坏死区域尤其明显。尽管在大多数情况下，肿瘤细胞未检测到 OPN mRNA 标记，但肿瘤细胞和巨噬细胞都对 OPN 蛋白进行了染色，这表明巨噬细胞分泌的 OPN 可能通过 OPN 中的甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸细胞结合结构域与肿瘤细胞结合。总的来说，这些数据表明 OPN 在肿瘤/宿主界面的粘附相互作用中发挥作用，从而可能影响侵袭和转移等过程。
Osteopontin (OPN), a secreted adhesive glycoprotein, is significantly overexpressed in a variety of experimental models of malignancy. Moreover, increased levels of OPN have been detected in the blood of patients with metastatic carcinoma. To investigate OPN expression and distribution in human carcinomas directly, we studied a wide variety of common tumors by Northern analysis, in situ hybridization, and immunohistochemistry. All 14 tumors studied by Northern analysis showed very substantial increases in OPN messenger (m)RNA when compared to corresponding normal tissues. Moreover, intense labeling for OPN mRNA was detected in 71 of 76 carcinomas studied by in situ hybridization. In most of the carcinomas studied (colon, stomach, duodenum, pancreas, breast, lung, bladder, prostate, ovary, thyroid, and melanoma), tumor cells did not label detectably for OPN mRNA; however, macrophages intimately associated with tumor cells labeled strongly for the OPN transcript. In carcinomas of the kidney and endometrium, both tumor cells and host macrophages labeled strongly for OPN mRNA. The presence of OPN mRNA in macrophages was particularly pronounced at the edge of tumors (ie, the tumor/stroma interface) and in areas of tumor necrosis. Although in most cases tumor cells did not label detectably for OPN mRNA, both tumor cells and macrophages stained for OPN protein, suggesting that OPN secreted by macrophages may bind to tumor cells, possibly through the glycine-arginine-glycine-aspartate-serine cell binding domain in OPN. Collectively, these data suggest that OPN functions in adhesive interactions at the tumor/host interface and thereby may influence processes such as invasion and metastasis.