The role of SDF-1α/CXCR4 signal in the lymph node metastases of early colon cancer.

• Project/Area Number: 21590382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Dokkyo Medical University
• Principal Investigator: IMURA Johji 獨協医科大学, 医学部, 准教授 (80316554)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸癌 / CXCR4 / SDF-1α / リンパ節転移 / 免疫組織化学 / 低酸素 / Hypoxia inducible factor / Laminin-5γ 2chain / 癌 / 病理学 / 遣伝子 / 臨床 / 転移 / 遺伝子

Research Abstract

The purpose of this study
The endoscopic resection with a low aggressiveness is expected from the treatment for patients of early colon cancer. However, they have been removed surgically until now though the risk of lymph node metastases are less than 10%. If the lymph node metastatic mechanism of colon cancer is elucidated and the marker to predict lymph node metastases is established, the patients of early colon cancer without lymph node metastasis might be cured by the endoscopic resection with low aggressiveness. Therefore, comparing between the expression of CXCR4 and of its ligand SDF-1α and the clinicopathological factorsin this study, I clarify whether both factors are an useful marker to predict the lymph node metastases in the early colon cancer.
The study design
Histopathological examination about the expression of CXCR4 and SDF-1α in the colon cancer tissue.
Localization of the expression in the tumor tissue:
Localization of the expression for CXCR4 and SDF-1α in the primary les ion of surgically resected specimens provided from colon cancer patients was immunohistochemically examined. The expression of both factors was compared about the correlation with lymph node metastases.
The examination for coexpressed factors:
The coexpression of Hypoxia inducible factor(HIF) to let overexpression of CXCR4 in hypoxic condition and Laminin-5γ2chain to be one of the basement membrane components were examined. The ability to dissociate from the neoplastic nest, the migration and the adhesion ability of tumor cells correlated with CXCR4/SDF-1αsignaling.
Correlation with the ability of migration and adhesion:
It was examined whether the CXCR4 overexpression colon cancer cells transfected using the expression vector affected the ability of migration and adhesion.
Similarly, it was considered whether the CXCR4 reduced cells by siRNA affect these phenomenon.
The expression of both factors examined the differences between the single layered colon cancer cells and the sphroid formed cells.

Research Products

• [Journal Article] IgG4-related plasmacytic enteropathy mimicking ulcerative colitis (2012)
  • Author(s): Imura J, Fujimori T
  • Journal Title: Int J Surg Pathol Volume: 20(1) Pages: 59-59
  • Peer Reviewed
• [Journal Article] Clinicopathological features of serrated adenocarcinoma defined by makinen in dukes' B colorectal carcinoma (2012)
  • Author(s): Shida Y, Fujimori T, Tanaka H, Fujimori Y, Kimura R, Ueda H, Ichikawa K, Tomita S, Nagata H, Kubota K, Tsubaki M, Kato H, Yao T, Sugai T, Sugihara K, Ohkura Y, Imura J
  • Journal Title: Pathobiology Volume: 79(4) Pages: 169-74
  • Peer Reviewed
• [Journal Article] Clinicopathological features of serrated adenocarcinoma defined by Makinen in dukes' B colorectal carcinoma (2012)
  • Author(s): Shida Y, 他
  • Journal Title: Pathobiolgy Volume: 79 Pages: 169-174
  • Peer Reviewed
• [Journal Article] IgG4-related plasmacytic enteropathy mimicking ulcerative colitis (2012)
  • Author(s): Imura J, 他
  • Journal Title: Int J Surg Pathol Volume: 20 Pages: 59-59
  • Peer Reviewed
• [Journal Article] Laparoscopic resection of epidermoid cyst arising from an intrapancreatic accessory spleen : a case report with a review of the literature (2011)
  • Author(s): Iwasaki Y, Tagaya N, Nakagawa A, Kita J, Imura J, Fujimori T, Kubota K
  • Journal Title: Surg Laparosc Endosc Percutan Tech Volume: 21(5) Pages: 275-9
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of REG Iαexpression in ulcerative colitis-associated neoplastic lesions (2011)
  • Author(s): Tanaka H, Fukui H, Fujii S, Sekikawa A, Yamagishi H, Ichikawa K, Tomita S, Imura J, Yasuda Y, Chiba T, Fujimori T
  • Journal Title: Digestion Volume: 83(3) Pages: 204-9
  • Peer Reviewed
• [Journal Article] Ectopic gastric mucosa and pancreatic ducts in the rectum (2011)
  • Author(s): Yamagishi H, Fukui H, Tomita S, Ichikawa K, Imura J, Ishizuka M, Kubota K, Fujimori T
  • Journal Title: Intern Med Volume: 50(15) Pages: 1587-9
  • NAID: 130000969353
  • Peer Reviewed
• [Journal Article] Peripancreatic paraganglioma : a potential diagnostic challenge in cytopathology and surgical pathology (2011)
  • Author(s): Singhi AD, Hruban RH, Fabre M, Imura J, Schulick R, Wolfgang C, Ali SZ
  • Journal Title: Am J Surg Pathol Volume: 35(10) Pages: 1498-504
  • Peer Reviewed
• [Journal Article] 医療の均霑化に向けての病理・細胞診の関わり (2011)
  • Author(s): 井村穣二, 木村隆輔, 内田好明, 市川一仁, 藤盛孝博
  • Journal Title: 病理と臨床 Volume: 29(12) Pages: 1376-8
• [Journal Article] DMBT1 is a novel gene induced by IL-22 in ulcerative colitis (2011)
  • Author(s): Fukui H, Sekikawa A, Tanaka H, Fujimori Y, Katake Y, Fujii S, Ichikawa K, Tomita S, Imura J, Chiba T, Fujimori T
  • Journal Title: Inflamm Bowel Dis Volume: 17(5) Pages: 1177-88
• [Journal Article] Immunohistochemical analysis of REG Iα expression in ulcerative colitis-associated neoplastic lesions (2011)
  • Author(s): Tanaka H, 他
  • Journal Title: Digestion Volume: 83 Pages: 204-209
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of REG 1α expression in ulcerative colitis-associated neoplastic lesions. (2011)
  • Author(s): Tanaka H., et al.
  • Journal Title: Digestion Volume: 83 Pages: 204-209
  • Peer Reviewed
• [Journal Article] Involvement of the IL-22/REG Ialpha axis in ulcerative colitis (2010)
  • Author(s): Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, Tomita S, Imura J, Shiratori K, Chiba T, Fujimori T
  • Journal Title: Lab Invest Volume: 90(3) Pages: 496-505
  • Peer Reviewed
• [Journal Article] Detection of desmoplastic reaction in biopsy specimens is useful for predicting the depth of invasion of early colorectal cancer : a Japanese collaborative study (2010)
  • Author(s): Hirose M, Fukui H, Igarashi Y, Fujimori Y, Katake Y, Sekikawa A, Ichikawa K, Tomita S, Imura J, Ajioka Y, Ueno H, Hase K, Ohkura Y, Kashida H, Togashi K, Nishigami T, Matsui T, Yao T, Wada R, Matsuda K, Watanabe T, Ochiai A, Sugai T, Sugihara K, Fujimori S
  • Journal Title: J Gastroenterol Volume: 45(12) Pages: 1212-8
  • NAID: 10027700032
  • Peer Reviewed
• [Journal Article] GROαpromotes invasion of colorectal cancer cells (2010)
  • Author(s): Ogata H, Sekikawa A, Yamagishi H, Ichikawa K, Tomita S, Imura J, Ito Y, Fujita M, Tsubaki M, Kato H, Fujimori T, Fukui H
  • Journal Title: Oncol Rep Volume: 24(6) Pages: 1479-86
  • Peer Reviewed
• [Journal Article] 術中迅速細胞診の普及に向けて (2010)
  • Author(s): 井村穣二, 常松一恵, 内田好明, 阿部香織, 新発田雅晴, 藤盛孝博
  • Journal Title: 病理と臨床 Volume: 28(12) Pages: 1312-4
• [Journal Article] GROα promotes invasion of colorectal cancer cells. (2010)
  • Author(s): Ogata H., et al.
  • Journal Title: Oncol Rep. Volume: 24 Pages: 1479-486
  • Peer Reviewed
• [Journal Article] Detection of desmoplastic reaction in biopsy specimens is useful for predicting the depth of invasion of early colorectal cancer : a Japanese collaborative study. (2010)
  • Author(s): Hirose M., et al.
  • Journal Title: J.Gastroenterol. Volume: 45 Pages: 1212-1218
  • Peer Reviewed
• [Journal Article] Expression profile of REG family proteins REG Ialpha and REG IV in advanced gastric cancer : comparison with mucin phenotype and prognostic markers (2009)
  • Author(s): Yamagishi H, Fukui H, Sekikawa A, Kono T, Fujii S, Ichikawa K, Tomita S, Imura J, Hiraishi H, Chiba T, Fujimori T
  • Journal Title: Mod Pathol Volume: 22(7) Pages: 906-13
  • Peer Reviewed
• [Journal Article] Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in Japanese patients with non-small-cell lung cancer (2009)
  • Author(s): Akasaka K
  • Journal Title: Cancer Chemother Pharmacol (In press)
  • Peer Reviewed
• [Journal Article] Expression of SDF-1α and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer (2008)
  • Author(s): Yoshitake N
  • Journal Title: Br J Cancer 98 Pages: 1682-1689
  • Peer Reviewed
• [Journal Article] Extrapancreatic F-18 FDG accumulation in autoimmune pancreatitis (2008)
  • Author(s): Sato M
  • Journal Title: Ann Nucl Med 22 Pages: 215-219
  • Peer Reviewed
• [Presentation] 乳癌におけるインスレーター機構としてのCTCF-1の役割 (2011)
  • Author(s): 井村穣二, 阿部香織, 冨田茂樹, 大竹真一郎, 市川一仁, 藤盛孝博
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋.名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] 藤盛孝博膵臓細胞診における質的診断向上への試み膵臓細胞診の質的精度向上に向けた新たな取り組み (2011)
  • Author(s): 井村穣二, 内田好昭, 安田真大, 古村祐紀, 阿部香織, 新発田雅晴, 小谷松寿美子, 米川伸生, 冨田茂樹
  • Organizer: 第52回日本臨床細胞学会総会
  • Place of Presentation: 福岡.福岡国際会議場
  • Year and Date: 2011-05-21
• [Presentation] 肝細胞癌における新たな癌幹細胞因子の探索 (2011)
  • Author(s): 井村穣二, 山岸秀嗣, 冨田茂樹, 市川一仁, 加藤洋, 藤盛孝博
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜.パシフィコ横浜
  • Year and Date: 2011-04-28
• [Presentation] 藤盛孝博分子診断に焦点を合わせた内膜病変の診断法、検査法分子診断を目的とした内膜病変におけるmethyl化異常の捕捉 (2010)
  • Author(s): 井村穣二, 阿部香織, 内田好明, 池田聡, 新発田雅晴, 常松一恵, 冨田茂樹, 飯嶋達生, 鈴木恵子
  • Organizer: 第49回日本臨床細胞学会秋季大会
  • Place of Presentation: 神戸.神戸ポートピアホテル
  • Year and Date: 2010-11-20
• [Presentation] 胆道・膵臓の細胞診今後の胆道・膵臓の細胞診に求められる期待に応えるための新たな探究 (2010)
  • Author(s): 井村穣二
  • Organizer: 第49回日本臨床細胞学会秋季大会
  • Place of Presentation: 神戸.神戸ポートピアホテル
  • Year and Date: 2010-11-20
• [Presentation] 子宮体部内膜癌の発生に関わる各種遺伝子のPromoter領域におけるMethylation状態の検討 (2010)
  • Author(s): 井村穣二, 斉藤仁昭, 冨田茂樹, 藤盛孝博
  • Organizer: 第57回日本臨床検査医学会
  • Place of Presentation: 東京.京王プラザホテル
  • Year and Date: 2010-08-28
• [Presentation] 今後の細胞診と応用可能な一工夫 (2010)
  • Author(s): 井村穣二
  • Organizer: 第51回日本臨床細胞学会総会
  • Place of Presentation: 東京.京王プラザホテル
  • Year and Date: 2010-05-30
• [Presentation] 胃癌・大腸癌(歴史をふまえて)大腸癌の発生・浸潤・転移に関わる遺伝子異常 (2010)
  • Author(s): 藤盛孝博, 他
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-28
• [Presentation] 膵癌Spheroid形成に関わる諸因子の検索 (2010)
  • Author(s): 井村穣二, 冨田茂樹, 市川一仁, 関川昭, 福井広一, 藤盛孝博
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京.京王プラザホテル
  • Year and Date: 2010-04-22
• [Book] 病理診断の流れとポイント癌診療指針のための病理診断プラクテイス食道癌・胃癌 (2011)
  • Author(s): 井村穣二, 藤盛孝博
  • Publisher: 中山書店
• [Book] びまん性星細胞腫,髄膜腫,退形成星細胞腫,膠芽腫,転移性脳腫瘍アトラス細胞診と病理診断 (2010)
  • Author(s): 井村穣二, 國実久秋
  • Publisher: 医学書院