Local Existence of Osteopontin Positive Tumor-Associated Macrophages in Colorectal Cancer Stroma as Risk Factors of Postoperative Hepatic Metastasis
Introduction: Metachronous hepatic metastasis following radical surgery for advanced colorectal cancer has a decisive influence on prognosis, thus screening of high risk patients is important. Osteopontin (OPN) is a phosphorylated glycoprotein with a cell adhesion sequence that is associated with tu...
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| Published in | Nippon Shokaki Geka Gakkai zasshi Vol. 40; no. 6; pp. 695 - 704 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
The Japanese Society of Gastroenterological Surgery
2007
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0386-9768 1348-9372 |
| DOI | 10.5833/jjgs.40.695 |
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| Abstract | Introduction: Metachronous hepatic metastasis following radical surgery for advanced colorectal cancer has a decisive influence on prognosis, thus screening of high risk patients is important. Osteopontin (OPN) is a phosphorylated glycoprotein with a cell adhesion sequence that is associated with tumor metastasis and proliferation.In the present study, we investigated the relationship between the incidence of hepatic metastasis and OPN expression using a immunohistochemical method in patients with colorectal cancer. Subjects and Methods: Patients with advanced colorectal cancer who underwent radical surgery were divided into 3 groups: those with synchronous hepatic metastasis (n=30), those with metachronous hepatic metastasis (n=17), and nonmetastatic cases (n=54). Immunohistochemical staining was performed using anti-OPN, CD68, and CD105 antibodies. Results: OPN expression was mainly observed in tumor associated macrophages (TAM) that had infiltrated the tumor surrounding the stroma, whereas it was not seen in the tumor cells. The ratios of OPN-positive TAM (OPN/TAM) and microvessel density (MVD) were determined for each location. As a result of univariate analysis in the metachronous hepatic metastasis group, significant differences were observed for the following 3 factors: MVD in the central area of the cancer stroma, and OPN/TAM ratios in the marginal and central areas. Results of multivariate analyses of those 3 suggested that the OPN/TAM ratios in the marginal and central areas of the cancer stroma might be risk factors for metachronous hepatic metastasis. Discussion: We concluded that OPN/TAM ratios in the cancer stroma in the marginal and central areas of excised colorectal specimens are useful for screening patients with a high risk of postoperative hepatic metastasis. |
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| AbstractList | Introduction: Metachronous hepatic metastasis following radical surgery for advanced colorectal cancer has a decisive influence on prognosis, thus screening of high risk patients is important. Osteopontin (OPN) is a phosphorylated glycoprotein with a cell adhesion sequence that is associated with tumor metastasis and proliferation.In the present study, we investigated the relationship between the incidence of hepatic metastasis and OPN expression using a immunohistochemical method in patients with colorectal cancer. Subjects and Methods: Patients with advanced colorectal cancer who underwent radical surgery were divided into 3 groups: those with synchronous hepatic metastasis (n=30), those with metachronous hepatic metastasis (n=17), and nonmetastatic cases (n=54). Immunohistochemical staining was performed using anti-OPN, CD68, and CD105 antibodies. Results: OPN expression was mainly observed in tumor associated macrophages (TAM) that had infiltrated the tumor surrounding the stroma, whereas it was not seen in the tumor cells. The ratios of OPN-positive TAM (OPN/TAM) and microvessel density (MVD) were determined for each location. As a result of univariate analysis in the metachronous hepatic metastasis group, significant differences were observed for the following 3 factors: MVD in the central area of the cancer stroma, and OPN/TAM ratios in the marginal and central areas. Results of multivariate analyses of those 3 suggested that the OPN/TAM ratios in the marginal and central areas of the cancer stroma might be risk factors for metachronous hepatic metastasis. Discussion: We concluded that OPN/TAM ratios in the cancer stroma in the marginal and central areas of excised colorectal specimens are useful for screening patients with a high risk of postoperative hepatic metastasis. |
| Author | Imano, Motohiro Shiozaki, Hitoshi Ishimaru, Eizaburo Ohyanagi, Harumasa Okuno, Kiyotaka |
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| References | 40) Shirouzu K, Isomoto H, Kakegawa T et al: A prospective clinicopathologic study of venous invasion in colorectal cancer. Am J Surg 162: 216-222, 1991 2) Wanebo HJ, Chu QD, Avradopoulos KA et al: Current perspective on repeat hepatic resection for colorectal carcinoma: a review. Surgery 119: 361-371, 1996 21) Sabattini E, Bisgaard K, Ascani S et al: The En Vision TM +system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, Chem Mate, CSA, sel growt LABC, and SABC techniques. J Clin Pathol 51: 506-511, 1998 34) Weber GF, Ashkar S, Glimcher MJ et al: Receptor-ligand interaction between CD 44 and osteopontin (Eta-1). Science 271: 509-512, 1996 43) Okuno K, Yasutomi M, Hida J et al: Longterm effects of heatic arterial interleukin-2-based immunochemotherapy after potentially curative resection of colorectal liver metastases. Am Coll Surg 187: 271-275, 1998 11) Senger DR, Ledbetter SR, Claffey KP et al: Stimulation of endothelial cell migration by vascular permeability facto/vascular endothelial growth factor through cooprative mechanisms involving the alphavbeta 3 integrin, osteopontin, and thrombin. Am J Pathol 149: 293-305, 1996 16) Maki M, Hirota S, Kaneko Y et al: Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cystadenocarcinoma: a possible association with calcification of psammoma bodies. Pathol Int 50: 531-535, 2000 35) Brown LF, Berse B, Van de Water L et al: Expression and distribution of osteopontin in human tissues; widespread association with luminal epithelial surfaces. Mol Biol cell 3: 1169-1180, 1992 20) 大腸癌研究会編: 大腸癌取扱い規約. 第6版. 金原出版, 東京, 1998 26) Takahashi Y, Kitadai Y, Bucana CD et al: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55: 3964-3968, 1995 41) Adachi Y, Inomata M, Kakisako K et al: Histopathologic characteristics of colorectal cancer with liver metastasis. Dis Colon Rectum 42: 1053-1056, 1999 13) Brown LF, Papadopoulos-Sergiou A, Berse B et al: Osteopontin expression and distribution in human carcinomas. Am J Pathol 145: 610-623, 1994 31) Pusztai L, Clover LM, Cooper K et al: Expression of tumour necrosis factor alpha and its receptors in carcinoma of the breast. Br J Cancer 70: 289-292, 1994 17) Gaumann A, Petrow P, Mentzel T et al: Osteopontin expression in primary sarcomas of the pulmonary artry. Virchows Arch 439: 668-674, 2001 28) Polverini PJ: Role of the macrophage in angiogenesis-dependent diseases. EXS 79: 11-28, 1997 38) Blood CH, Zetter BR: Tumor interactions with the vascularture: angiogenesis and tumor metastasis. Biochim Biophys Acta 1032: 89-118, 1990 7) Choti MA, Sitzmann JV, Tiburi MF et al: Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 235: 759-766, 2002 14) Shijubo N, Ueda T, Kon S et al: Vascular endothlial growth factor and osteopontin in stage I lung adenocarcinoma. Am J Respir Crit Care Med 160: 1269-1273, 1999 10) Denhardt DT, Lopez CA, Rollo EE et al: Osteopontin-induced modifications of cellular functions. Ann N Y Acad Sci 760: 127-142, 1995 12) Denhardt DT, Guo X: Osteopontin: a protein with diverse functions. FASEB J 7: 1475-1482, 1993 22) Bobrow MN, Harris TD, Shaughnessy KJ et al: Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays. J Immunol 125: 279-285, 1989 29) Leek RD, Harris AL, Lewis CE: Cytokine networks in solid human tumors: regulation of angi ogenesis. J Leukoc Biol 56: 423-435, 1994 25) Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442-447, 1987 24) Folkman J: How is blood vesh regulated in normal and neoplastic tissue ? G. H. A Clowes Memorial Award Lecture. Cancer Res 46: 467-473, 1986 23) ダコ・ジャパン株式会社: ENVISION+, ENVISION/APを使用した二重染色法. Immunohistochemistry. http//www.dako.jp/ihc/tec/dbsp. htm. 2007-01-16 1) Galandiuk S, Wieand HS, Moertel CG et al: Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet 174: 27-32, 1992 32) Ross FP, Chappel J, Alvarez JI et al: Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin &vβ3 potentiate bone resorption. J Biol Chem 268: 9901-9907, 1993 5) Fong Y, Fortner J, Sun RL et al: Clinical score for predicting recurrence afte hepatic resection for metastatic colorectal cancer. Ann Surg 230: 309-321, 1999 33) Smith LL, Cheung HK, Ling LE et al: Osteopntin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin. J Biol Chem 271: 28485-28491, 1996 39) Akagi K, Ikeda Y, Sumiyoshi Y et al: Estimation of angiogenesis with anti-CD105 immunostainig in the process of colorectal cancer development. Surgery 131: 109-113, 2002 19) Mantovani A: Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab Invest 71: 5-16, 1994 37) Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364, 1996 36) Ohtani H, Naito K, Saito K et al: Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity? Lab Invest 77: 231-243, 1997 42) Yamada H, Kondo S, Okushiba S et al: Analysis of predictive factors for recurrence after for colorectal liver metastases. World J Surg 25: 1129-1133, 2001 8) 安井健三, 清水泰博, 平井孝ほか: 大腸癌肝転移の外科治療, 多施設における根治的肝切除例の検討. 癌と化療31: 690-694, 2004 27) Leek RD, Lewis CE, Whitehouse R et al: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56: 4625-4629, 1996 15) Tuck AB, O.Malley FP, Singhal H et al: Osteo pontin expression in a group of lymph node negative breast cancer patients. Int J Cancer 79: 502-508, 1998 30) Baird A, Mormede P, Bohlen P: Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophagederived growth factor. Biochem Biophys Res Commun 126: 358-364, 1985 4) Sugihara K, Hojo K, Moriya Y et al: Pattern of recurrence after hepatic resection for colorectal metastases. Br J Surg 80: 1032-1035, 1993 3) Nordlinger B, Guiguet M, Vaillant J et al: Surgical resection of colorectal carcinoma metastases to the liver; a prognostic scoring system to improve case selection, based on 1,568 patients. Cancer 77: 1254-1262, 1996 9) Oldberg A, Franzen A, Heinegard D: Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cellbinding sequence. Proc Natl Acad Sci USA 83: 8819-8823, 1986 6) Minagawa M, Makuuchi M, Torzilli G et al: Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer; long-term results. Ann Surg 231: 487-499, 2000 18) Zhang J, Takahashi K, Takahashi F et al: Differential osteopontin expression in lung cancer. Cancer Lett 171: 215-222, 2001 |
| References_xml | – reference: 12) Denhardt DT, Guo X: Osteopontin: a protein with diverse functions. FASEB J 7: 1475-1482, 1993 – reference: 9) Oldberg A, Franzen A, Heinegard D: Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cellbinding sequence. Proc Natl Acad Sci USA 83: 8819-8823, 1986 – reference: 30) Baird A, Mormede P, Bohlen P: Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophagederived growth factor. Biochem Biophys Res Commun 126: 358-364, 1985 – reference: 5) Fong Y, Fortner J, Sun RL et al: Clinical score for predicting recurrence afte hepatic resection for metastatic colorectal cancer. Ann Surg 230: 309-321, 1999 – reference: 42) Yamada H, Kondo S, Okushiba S et al: Analysis of predictive factors for recurrence after for colorectal liver metastases. World J Surg 25: 1129-1133, 2001 – reference: 7) Choti MA, Sitzmann JV, Tiburi MF et al: Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 235: 759-766, 2002 – reference: 29) Leek RD, Harris AL, Lewis CE: Cytokine networks in solid human tumors: regulation of angi ogenesis. J Leukoc Biol 56: 423-435, 1994 – reference: 38) Blood CH, Zetter BR: Tumor interactions with the vascularture: angiogenesis and tumor metastasis. Biochim Biophys Acta 1032: 89-118, 1990 – reference: 28) Polverini PJ: Role of the macrophage in angiogenesis-dependent diseases. EXS 79: 11-28, 1997 – reference: 6) Minagawa M, Makuuchi M, Torzilli G et al: Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer; long-term results. Ann Surg 231: 487-499, 2000 – reference: 41) Adachi Y, Inomata M, Kakisako K et al: Histopathologic characteristics of colorectal cancer with liver metastasis. Dis Colon Rectum 42: 1053-1056, 1999 – reference: 15) Tuck AB, O.Malley FP, Singhal H et al: Osteo pontin expression in a group of lymph node negative breast cancer patients. Int J Cancer 79: 502-508, 1998 – reference: 4) Sugihara K, Hojo K, Moriya Y et al: Pattern of recurrence after hepatic resection for colorectal metastases. Br J Surg 80: 1032-1035, 1993 – reference: 18) Zhang J, Takahashi K, Takahashi F et al: Differential osteopontin expression in lung cancer. Cancer Lett 171: 215-222, 2001 – reference: 36) Ohtani H, Naito K, Saito K et al: Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity? Lab Invest 77: 231-243, 1997 – reference: 8) 安井健三, 清水泰博, 平井孝ほか: 大腸癌肝転移の外科治療, 多施設における根治的肝切除例の検討. 癌と化療31: 690-694, 2004 – reference: 33) Smith LL, Cheung HK, Ling LE et al: Osteopntin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin. J Biol Chem 271: 28485-28491, 1996 – reference: 21) Sabattini E, Bisgaard K, Ascani S et al: The En Vision TM +system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, Chem Mate, CSA, sel growt LABC, and SABC techniques. J Clin Pathol 51: 506-511, 1998 – reference: 13) Brown LF, Papadopoulos-Sergiou A, Berse B et al: Osteopontin expression and distribution in human carcinomas. Am J Pathol 145: 610-623, 1994 – reference: 24) Folkman J: How is blood vesh regulated in normal and neoplastic tissue ? G. H. A Clowes Memorial Award Lecture. Cancer Res 46: 467-473, 1986 – reference: 16) Maki M, Hirota S, Kaneko Y et al: Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cystadenocarcinoma: a possible association with calcification of psammoma bodies. Pathol Int 50: 531-535, 2000 – reference: 19) Mantovani A: Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab Invest 71: 5-16, 1994 – reference: 32) Ross FP, Chappel J, Alvarez JI et al: Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin &vβ3 potentiate bone resorption. J Biol Chem 268: 9901-9907, 1993 – reference: 43) Okuno K, Yasutomi M, Hida J et al: Longterm effects of heatic arterial interleukin-2-based immunochemotherapy after potentially curative resection of colorectal liver metastases. Am Coll Surg 187: 271-275, 1998 – reference: 26) Takahashi Y, Kitadai Y, Bucana CD et al: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55: 3964-3968, 1995 – reference: 27) Leek RD, Lewis CE, Whitehouse R et al: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56: 4625-4629, 1996 – reference: 39) Akagi K, Ikeda Y, Sumiyoshi Y et al: Estimation of angiogenesis with anti-CD105 immunostainig in the process of colorectal cancer development. Surgery 131: 109-113, 2002 – reference: 11) Senger DR, Ledbetter SR, Claffey KP et al: Stimulation of endothelial cell migration by vascular permeability facto/vascular endothelial growth factor through cooprative mechanisms involving the alphavbeta 3 integrin, osteopontin, and thrombin. Am J Pathol 149: 293-305, 1996 – reference: 31) Pusztai L, Clover LM, Cooper K et al: Expression of tumour necrosis factor alpha and its receptors in carcinoma of the breast. Br J Cancer 70: 289-292, 1994 – reference: 20) 大腸癌研究会編: 大腸癌取扱い規約. 第6版. 金原出版, 東京, 1998 – reference: 2) Wanebo HJ, Chu QD, Avradopoulos KA et al: Current perspective on repeat hepatic resection for colorectal carcinoma: a review. Surgery 119: 361-371, 1996 – reference: 23) ダコ・ジャパン株式会社: ENVISION+, ENVISION/APを使用した二重染色法. Immunohistochemistry. http//www.dako.jp/ihc/tec/dbsp. htm. 2007-01-16 – reference: 3) Nordlinger B, Guiguet M, Vaillant J et al: Surgical resection of colorectal carcinoma metastases to the liver; a prognostic scoring system to improve case selection, based on 1,568 patients. Cancer 77: 1254-1262, 1996 – reference: 1) Galandiuk S, Wieand HS, Moertel CG et al: Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet 174: 27-32, 1992 – reference: 22) Bobrow MN, Harris TD, Shaughnessy KJ et al: Catalyzed reporter deposition, a novel method of signal amplification. Application to immunoassays. J Immunol 125: 279-285, 1989 – reference: 25) Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442-447, 1987 – reference: 35) Brown LF, Berse B, Van de Water L et al: Expression and distribution of osteopontin in human tissues; widespread association with luminal epithelial surfaces. Mol Biol cell 3: 1169-1180, 1992 – reference: 40) Shirouzu K, Isomoto H, Kakegawa T et al: A prospective clinicopathologic study of venous invasion in colorectal cancer. Am J Surg 162: 216-222, 1991 – reference: 17) Gaumann A, Petrow P, Mentzel T et al: Osteopontin expression in primary sarcomas of the pulmonary artry. Virchows Arch 439: 668-674, 2001 – reference: 10) Denhardt DT, Lopez CA, Rollo EE et al: Osteopontin-induced modifications of cellular functions. Ann N Y Acad Sci 760: 127-142, 1995 – reference: 34) Weber GF, Ashkar S, Glimcher MJ et al: Receptor-ligand interaction between CD 44 and osteopontin (Eta-1). Science 271: 509-512, 1996 – reference: 37) Hanahan D, Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364, 1996 – reference: 14) Shijubo N, Ueda T, Kon S et al: Vascular endothlial growth factor and osteopontin in stage I lung adenocarcinoma. Am J Respir Crit Care Med 160: 1269-1273, 1999 |
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| Title | Local Existence of Osteopontin Positive Tumor-Associated Macrophages in Colorectal Cancer Stroma as Risk Factors of Postoperative Hepatic Metastasis |
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