Analysis of epigenetic alterations in tumor stromal cells and application in cancer diagnosis and treatment.

• Project/Area Number: 15K08383
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: HABANO WATARU 岩手医科大学, 薬学部, 准教授 (50332979)
• Co-Investigator(Renkei-kenkyūsha): Sugai Tamotsu 岩手医科大学, 医学部, 教授 (20187628)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 癌間質 / 腺管分離法 / エピジェネティクス

Outline of Final Research Achievements

Genetic alterations accumulate in crypt epithelial cells during colorectal carcinogenesis. We focused on the role of stromal tissue surrounding tumor epithelial cells. Crypt and stromal compartments were isolated from both normal and tumor tissues surgically resected from 2 patients with colorectal cancer, and global DNA methylation profiles were compared among these tissues. Different DNA methylation profile between normal and tumor crypts reveled certain genes responsible for colorectal cancer. Interestingly, there were few, but significant numbers of genes that showed different DNA methylation status between normal and tumor stroma. This suggests that alterations of not only epithelial cells, but also stromal cells, play important roles in colorectal carcinogenesis through an epigenetic mechanism.

Research Products

• [Journal Article] Molecular profiling and genome-wide analysis based on somatic copy number alterations in advanced colorectal cancers (2018)
  • Author(s): Sugai T, Takahashi Y, Eizuka M, Sugimoto R, Fujita Y, Habano W, Otsuka K, Sasaki A, Yamamoto E, Matsumoto T, Suzuki H.
  • Journal Title: Molecular Carcinogenesis Volume: 57 Issue: 3 Pages: 451-461
  • DOI: 10.1002/mc.22769
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the DNA methylation level of cancer-related genes in colorectal cancer and the surrounding normal mucosa. (2017)
  • Author(s): Sugai T, Yoshida M, Eizuka M, Uesugii N, Habano W, Otsuka K, Sasaki A, Yamamoto E, Matsumoto T, Suzuki H.
  • Journal Title: Clin Epigenetics. Volume: 55 Issue: 1 Pages: 55-55
  • DOI: 10.1186/s13148-017-0352-4
  • Peer Reviewed / Open Access
• [Journal Article] Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays. (2017)
  • Author(s): Eizuka M, Sugai T, Habano W, Uesugi N, Takahashi Y, Kawasaki K, Yamamoto E, Suzuki H, Matsumoto T.
  • Journal Title: J Gastroenterol Volume: - Issue: 11 Pages: 1158-1168
  • DOI: 10.1007/s00535-017-1317-2
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of molecular alterations in laterally spreading tumors of the colorectum. (2017)
  • Author(s): Sugai T, Habano W, Takagi R, Yamano H, Eizuka M, Arakawa N, Takahashi Y, Yamamoto E, Kawasaki K, Yanai S, Ishida K, Suzuki H, Matsumoto T.
  • Journal Title: J Gastroenterol Volume: 52 Issue: 6 Pages: 715-723
  • DOI: 10.1007/s00535-016-1269-y
  • NAID: 110006550042
  • Peer Reviewed / Open Access
• [Journal Article] Molecular subtypes of colorectal cancers determined by PCR-based analysis. (2017)
  • Author(s): Sugai T, Eizuka M, Takahashi Y, Fukagawa T, Habano W, Yamamoto E, Akasaka R, Otuska K, Matsumoto T, Suzuki H.
  • Journal Title: Cancer Sci Volume: 108(3) Issue: 3 Pages: 427-434
  • DOI: 10.1111/cas.13164
  • Peer Reviewed / Open Access
• [Journal Article] Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer. (2016)
  • Author(s): Takahashi Y, Sugai T, Habano W, Ishida K, Eizuka M, Otsuka K, Sasaki A, Matsumoto T, Morikawa T, Unno M, Suzuki H.
  • Journal Title: Int J Cancer Volume: 139 Issue: 11 Pages: 2493-2501
  • DOI: 10.1002/ijc.30377
  • Peer Reviewed / Open Access
• [Journal Article] Combination of the histone deacetylase inhibitor depsipeptide and 5-fluorouracil upregulates major histocompatibility complex class II and p21 genes and activates caspase-3/7 in human colon cancer HCT-116 cells. (2016)
  • Author(s): Okada K, Hakata S, Terashima J, Gamou T, Habano W, Ozawa S
  • Journal Title: Oncol Rep Volume: 36(4) Issue: 4 Pages: 1875-1885
  • DOI: 10.3892/or.2016.5008
  • Peer Reviewed
• [Journal Article] Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability-high phenotype (2016)
  • Author(s): Sugimoto R, Sugai T, Habano W, Endoh M, Eizuka M, Yamamoto E, Uesugi N, Ishida K, Kawasaki T, Matsumoto T, Suzuki H.
  • Journal Title: Int J Cancer Volume: 1 Issue: 7 Pages: 1689-97
  • DOI: 10.1002/ijc.29916
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of DNA methylation landscape reveals the roles of DNA methylation in the regulation of drug metabolizing enzymes (2015)
  • Author(s): Habano W, Kawamura K, Iizuka N, Terashima J, Sugai T, Ozawa S.
  • Journal Title: Clinical Epigenetics Volume: 7 Issue: 1 Pages: 105-105
  • DOI: 10.1186/s13148-015-0136-7
  • Peer Reviewed / Open Access
• [Journal Article] CYP1A1 and CYP1A2 expression levels are differentially regulated in three-dimensional spheroids of liver cancer cells compared to two-dimensional monolayer cultures (2015)
  • Author(s): Terashima J, Goto S, Hattori H, Hoshi S, Ushirokawa M, Kudo K, Habano W, Ozawa S.
  • Journal Title: Drug Metab Pharmacokinet. Volume: 30 Issue: 6 Pages: 434-440
  • DOI: 10.1016/j.dmpk.2015.10.001
  • NAID: 50014429984
  • Peer Reviewed
• [Journal Article] A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'-flanking region of rat cytochrome P450 (CYP) 3A1 gene (2015)
  • Author(s): Gamou T, Habano W, Terashima J, Ozawa S.
  • Journal Title: Drug Metab Pharmacokinet. Volume: 30 Issue: 2 Pages: 188-197
  • DOI: 10.1016/j.dmpk.2014.12.008
  • NAID: 210000171579
  • Peer Reviewed
• [Presentation] DNAメチル基転移酵素阻害剤併用によるヒト大腸がん細胞株のイリノテカン感受性増強とアポトーシス関連タンパクの発現変動 (2016)
  • Author(s): 博多修子、寺島潤、幅野渉、小澤正吾
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] AhRの肺がん細胞における遺伝子発現制御の解析 (2016)
  • Author(s): 神馬瑤子、寺島潤、幅野渉、小澤正吾
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Analysis of DNA methylation landscape reveals the roles of DNA methylation in the regulation of drug metabolizing enzymes (2015)
  • Author(s): 幅野渉、寺島潤、小澤正吾
  • Organizer: 日本薬物動態学会第30回年回
  • Place of Presentation: 東京
  • Year and Date: 2015-11-12