Molecular and pathology analyses for switching mechanism of stromal inducement in invasive oral carcinoma

• Project/Area Number: 18390486
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Niigata University
• Principal Investigator: SAKU Takashi Niigata University, 医歯学系, 教授 (40145264)
• Co-Investigator(Kenkyū-buntansha): CHENG Jun 新潟大学, 医歯学系, 准教授 (40207460) ; MARUYAMA Satoshi 新潟大学, 医歯学総合病院, 講師 (30397161) ; SUZUKI Makoto 新潟大学, 医歯学総合病院, 講師 (50107778) ; IDA Hiroko 新潟大学, 医歯学総合病院, 講師 (60293213)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,450,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥3,150,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2006: ¥4,800,000 (Direct Cost: ¥4,800,000)
• Keywords: 口腔癌細胞 / 浸潤 / 間質誘導 / 細胞外基質 / 産生担当スイッチング / スイッチング / 細胞外基質分泌障害 / レーザチャプチャー / RT-PCR / 蛍光抗体法

Research Abstract

扁平上皮癌の腫瘍性間質誘導が、浸潤を契機に実質細胞から間質細胞に移管される(スイッチング)のではないかという仮説をたて、これを証明するために扁平上皮癌細胞と線維芽細胞の共培養系を作製して、細胞外基質分子代謝を軸に検討し、口腔癌組織の結果と照合した.その結果、上皮内癌に相当する分離共培養では癌細胞側に、浸潤癌に相当する混合共培養では、線維芽細胞側にECM 産生の主体があり、間質誘導が扁平上皮癌浸潤によって開始することを証明し、この概念を病理診断の理論的背景として適用することに成功した.この結果、非浸潤性腫瘍の腫瘍細胞間隙の細胞外基質を腫瘍細胞によって産生される上皮内基質という概念でとらえることを提唱することになった.

Research Products

• [Journal Article] Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas (2009)
  • Author(s): Maruyama S, Cheng J, Yamazaki M, Liu A, Saku T
  • Journal Title: J Oral Pathol Med 38(4) Pages: 377-385
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ : and aid for histopathologic recognition of their cell proliferation centers (2009)
  • Author(s): Tilakaratne WM, Kobayashi T, Ida-Yonemochi H, Swelam W, Yamazaki M, Mikami T, Alvarado CG, Shahidul AM, Maruyama S, Cheng J, Saku T
  • Journal Title: J Oral Pathol Med 38(4) Pages: 348-355
  • Peer Reviewed
• [Journal Article] FGF/KGF enhances proliferation but suppresses invasion of adenoid cystic carcinoma (2008)
  • Author(s): Maruyama S, Cheng J, Saku T
  • Journal Title: Oral Oncology 12(1) Pages: 243-250
  • Peer Reviewed
• [Journal Article] Perlecan-rich epithelial linings as a background of proliferative potentials of Keratocystic odontogenic tumor (2008)
  • Author(s): Tsuneki M, Cheng J, Maruyama S, Ida-Yonemochi H, Nakajima M, Saku T
  • Journal Title: J Oral Pathol Med 37(5) Pages: 287-293
  • Peer Reviewed
• [Journal Article] 口腔粘膜表在性癌 (2008)
  • Author(s): 朔敬
  • Journal Title: 病理と臨床 26(6) Pages: 548-561
  • Peer Reviewed
• [Journal Article] Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas (2008)
  • Author(s): Maruyama S
  • Journal Title: Journal of Oral Pathology & Medicine 38
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ : an aid for histopathologic recognition of their cell proliferation centers (2008)
  • Author(s): Tilakaratne WM
  • Journal Title: Journal of Oral Pathology & Medicine 38
  • Peer Reviewed
• [Journal Article] FGF7/KGF enhances proliferation but suppresses invasion of adenoid cystic carcinoma cells (2008)
  • Author(s): Maruyama S
  • Journal Title: Oral Oncology 12(1) Pages: 243-250
  • Peer Reviewed
• [Journal Article] Perlecan-rich epithelial lining as a background of proliferative potentials of keratocystic odontogenic tumor (2008)
  • Author(s): Tsuneki M
  • Journal Title: Journal of Oral Pathology & Medicine 37(5) Pages: 287-293
  • Peer Reviewed
• [Journal Article] Fine needle aspiration cytology of basal cell adenoma of the salivary gland (2007)
  • Author(s): Hara H, Oyama T, Saku T
  • Journal Title: Acta Cytol 51(5) Pages: 685-691
  • Peer Reviewed
• [Journal Article] High relative frequency of oral squamous cell carcinoma in Yemen : qat and tobacco chewing as its aetiological background (2007)
  • Author(s): Sawair FA, Al-Mutwakei A, Al-Eryani K, Al-Surhy A, Maruyama S, Cheng J, Al-Sharabi A, Saku T
  • Journal Title: Int J Environ Health Res 17(3) Pages: 185-195
  • Peer Reviewed
• [Journal Article] Lymphatic involvement in the histopathogenesis of mucous retention cyst (2007)
  • Author(s): Kundu S, Cheng J, Maruyama S, Suzuki M, Kawashima H, Saku T
  • Journal Title: Pathol Res Pract 203(2) Pages: 89-97
  • Peer Reviewed
• [Journal Article] Fine needle aspiration cytology of basal cell adenoma of the salivary gland (2007)
  • Author(s): Hara H
  • Journal Title: Acta Cytologica 51(5) Pages: 685-691
  • Peer Reviewed
• [Journal Article] High relative frequency of oral squamous cell carcinoma in Yemen: Qat and tobacco chewing as its aetiological background (2007)
  • Author(s): Sawair FA
  • Journal Title: International Journal of Environmental Health Research 17(3) Pages: 185-195
  • Peer Reviewed
• [Journal Article] Lymphatic involvement in the histopathogenesis of mucous retention cyst (2007)
  • Author(s): Kundu S
  • Journal Title: Pathol Res Pract 203(2) Pages: 89-97
• [Journal Article] Oral submucous fibrosis : review on aetiology and pathogenesis (2006)
  • Author(s): Tilakaratne WM. Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S
  • Journal Title: Oral Oncol 42(6) Pages: 561-568
  • Peer Reviewed
• [Journal Article] Perlecan, a heparan sulfate proteoglycan, is a major constituent of the intraepithelial stroma functioning in tooth morphogenesis (2006)
  • Author(s): Ida-Yonemochi H, Saku T
  • Journal Title: J Oral Biosc 48(4) Pages: 233-243
  • NAID: 10027102118
  • Peer Reviewed
• [Journal Article] Oral submucous fibrosis : review no aetiology and pathogenesis (2006)
  • Author(s): Tilakaratne WM
  • Journal Title: Oral Oncol 42(6) Pages: 561-568
• [Journal Article] Differential expression modes of matrix metalloproteinases (MMPs) in oral borderline malignancies : an aid for histopathological recognition of dysplastic cell zone (2006)
  • Author(s): Tilakaratne WM
  • Journal Title: Oral Med Pathol 11(1) Pages: 41-41
• [Journal Article] Perlecan, a heparan sulfate proteoglycan, is a major constituent of the intraepithelial stroma functioning in tooth morophogenesis (2006)
  • Author(s): Ida-Yonemochi H, et al.
  • Journal Title: J Oral Biosc 48(4) Pages: 233-243
• [Journal Article] 口腔粘膜上皮悪性境界病変におけるいわゆる幹細胞マーカ分子の発現様式 (2006)
  • Author(s): 小林孝憲
  • Journal Title: 日本口腔病理学会会誌 95(1) Pages: 288-288
• [Journal Article] 腺様嚢胞癌の転移におけるKGFの発現動態 (2006)
  • Author(s): 丸山 智
  • Journal Title: 日本口腔病理学会会誌 95(1) Pages: 288-288
• [Presentation] Recurrence of leukoplakias as evidence for malignancy : histopathological varieties of oral carcinoma in-situ. Asia- Pacific Congress on Oral Cancer (2008)
  • Author(s): Saku T
  • Organizer: 12^<th> Annual Meeting of Taiwan Cooperative Oncology Group
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Clinical and histological manifestation of oral lesion (2008)
  • Author(s): Saku T
  • Organizer: 3^<rd> Indonesian Scientific Meeting and Exhibition for Dentistry
  • Place of Presentation: Jember, Indonesia
• [Presentation] Histopathological diagnosis for oral cancer and precancer (2008)
  • Author(s): Saku T
  • Organizer: Asian Association of Oral and Maxillofacial Surgeons Lectures and Workshop
  • Place of Presentation: Bali, Indonesia
• [Presentation] New Histopathological criteria for oral borderline malignancies (2008)
  • Author(s): Saku T
  • Organizer: First Clinical Pathology Conference of the Chinese Academy of Oral Pathology
  • Place of Presentation: Hangzhou, China
• [Presentation] ジストログリカンはマウス歯胚エナメル器細胞においてパールカン受容体として機能している (2008)
  • Author(s): 依田浩子, 朔敬
  • Organizer: 第50回歯科基礎医学会
  • Place of Presentation: 東京都
• [Presentation] Multiple signaling pathways for perlecan in adenoid cystic carcinoma (2008)
  • Author(s): Ahsan S, Cheng J, Maruyama S, Ida-Yonemochi H, Saku T
  • Organizer: 第19回日本臨床口腔病理学会総会
  • Place of Presentation: 東京都
• [Presentation] Differential distribution modes of perlecan receptors, dystroglycan and integrin β1, in ameloblastomas (2008)
  • Author(s): Ida-Yonemochi H, Ahsan S, Saku T
  • Organizer: 14^<th> International Congress, International Association of Oral Pathologists
  • Place of Presentation: San Francisco, USA
• [Presentation] Survival of salivary pleomorphic adenoma cells in hypoxic condition (2008)
  • Author(s): Maruyama S, Cheng J, Saku T
  • Organizer: 14^<th> International Congress, International Association of Oral Pathologists
  • Place of Presentation: San Francisco, USA
• [Presentation] Pathologenesis of round-shaped dyskeratosis in oral CIS (2008)
  • Author(s): Al-Eryani K, Maruyama S, Cheng J, Saku T
  • Organizer: 14^<th> International Congress, International Association of Oral Pathologists
  • Place of Presentation: San Francisco, USA
• [Presentation] FGF7/KGF enhances proliferation but suppresses invasion of adenoid cystic carcinoma cells (2008)
  • Author(s): Maruyama S, Cheng J, Zhou XJ, Chen WT, Zhang ZY, Li J, Saku T
  • Organizer: International Congress on Oral Cancer
  • Place of Presentation: Shanghai, China
• [Presentation] 小唾液腺粘表皮癌の発生背景としての口腔粘膜前癌病変 (2008)
  • Author(s): 依田浩子, 小林孝憲, 丸山智, 程〓, 朔敬
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
• [Presentation] 口腔粘膜扁平上皮癌・上皮内癌の再発に関する臨床病理学的検討 (2008)
  • Author(s): 小林孝憲, 依田浩子, 丸山智, 程〓, 齋藤力, 高木律男, 朔敬
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
• [Presentation] Comparative expression modes of dystroglycan and perlecan in oral carcinoma in-situ (2008)
  • Author(s): Ahsan S, Cheng J, Maruyama S, Ida-Yonemochi H, Kobayashi T, Al-Eryani K, Mikami T, Saku T
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
• [Presentation] Immunohistochemical characterization of the two-phase appearance of oral precancerous lesion (2008)
  • Author(s): Alvarado C, Cheng J, Maruyama S, Ida-Yonemochi H, Al-Eryani K, Ahsan S, Kundu S, Saku T
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市
• [Presentation] Survival of salivary pleomorphic adenoma cells in hypoxic condition (2008)
  • Author(s): Maruyama S
  • Organizer: 14^<th> International Congress, International Associationof Oral Pathologists
  • Place of Presentation: San Francisco, USA
• [Presentation] Pathologenesis of round-shaped dyskeratosis in oral carcinoma in-situ (2008)
  • Author(s): Al-Eryani K
  • Organizer: 14^<th> International Congress, International Association of Oral Pathologists
  • Place of Presentation: San Francisco, USA
• [Presentation] FGF7/KGF enhances proliferation but suppresses invasion of adenoid cystic carcinoma cells (2008)
  • Author(s): Maruyama S
  • Organizer: 12^<th>International Congress on Oral Cancer
  • Place of Presentation: Shanghai, China
• [Presentation] New parenchymal-stromal switching for extracellular matrix production : conceptual evidence for the histopathological judgment of micro-invasive of oral squamous cell carcinomas (2007)
  • Author(s): Saku T
  • Organizer: The 3^<rd> Meeting of the Asian Society of Oral and Maxillofacial Pathology
  • Place of Presentation: Taipei, Taiwan
• [Presentation] 扁平上皮幹細胞またはがん幹細胞の概念と口腔粘膜上皮内癌の病理診断の立場 (2007)
  • Author(s): 朔敬
  • Organizer: 第17回日本口腔粘膜学会総会・学術集会
  • Place of Presentation: 東京都
• [Presentation] 腺様嚢胞癌細胞におけるKGFは細胞遊走を抑制して細胞増殖を促進している (2007)
  • Author(s): 丸山智, 程〓, 朔敬
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪市
• [Presentation] A possible role of retinoid signals in keratin expression profiles of oral carcinoma in-situ (2007)
  • Author(s): Kundu S, Mikami T, Maruyama S, Funayama A, Ahsan S, Alvarado C, Al-Eryani K, Cheng J, Kawashima H, Saku T
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪市
• [Presentation] 口腔粘膜扁平上皮癌のポドプラニン発現様式は悪性化進行度に対応している (2007)
  • Author(s): 船山昭典, 程〓, 丸山智, 新垣晋, 齊藤力, 朔敬
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪市
• [Presentation] 扁平上皮幹細胞またはがん幹細胞の概念と口腔粘膜上皮内癌の病理診断の立場 (2007)
  • Author(s): 朔 敬
  • Organizer: 第17回日本口腔粘膜学会学術大会
  • Place of Presentation: 東京都
• [Presentation] 口腔上皮内癌の診断に有効なケラチン組織化学 (2007)
  • Author(s): 三上俊彦
  • Organizer: 第18回日本口腔病理学会学術大会
  • Place of Presentation: 岐阜市
• [Presentation] 皮膚創傷治癒における上皮再生はパールカンで促進される (2007)
  • Author(s): 依田浩子
  • Organizer: 第49回歯科基礎医学会学術大会
  • Place of Presentation: 札幌市
• [Presentation] 口腔扁平上皮癌のいわゆる癌真珠の免疫組織化学的検討 (2007)
  • Author(s): 三上俊彦
  • Organizer: 第49回歯科基礎医学会学術大会
  • Place of Presentation: 札幌市
• [Presentation] New parenchymal-stromal switching for extracellular matrix production: conceptual evidence for the histopathological judgment of micro-invasive of oral squamous cell carcinomas (2007)
  • Author(s): Saku T
  • Organizer: The 3rd Meeting of the Asian Society of Oral and Maxillofacial Pathology
  • Place of Presentation: Taibei, Taiwan
• [Presentation] パールカン過剰発現系トランスジェニックマウスにおける脱毛現象の解析 (2006)
  • Author(s): 依田浩子, 里方一郎, 朔敬
  • Organizer: 第47回歯科基礎医学会
  • Place of Presentation: 横浜市
• [Presentation] 角化嚢胞性歯原性腫瘍の細胞増殖背景としての被覆上皮層内パールカン沈着 (2006)
  • Author(s): 常木雅之, 丸山智, 程〓, 鈴木誠, 朔敬
  • Organizer: 第47回歯科基礎医学会
  • Place of Presentation: 横浜市
• [Presentation] 唾液腺多形性腺腫における被膜浸潤と血管侵襲 (2006)
  • Author(s): 丸山智, 程〓, 朔敬
  • Organizer: 第17回日本口腔病理学会学術大会
  • Place of Presentation: 新潟市
• [Presentation] 口腔粘膜上皮内癌の特徴的上皮層内血管侵入とリンパ管反応 (2006)
  • Author(s): 船山昭典, 程〓, 丸山智, 新垣晋, 齊藤力, 朔敬
  • Organizer: 第17回日本口腔病理学会学術大会
  • Place of Presentation: 新潟市
• [Presentation] ヒト末梢血リンパ球およびパールカンとジストログリカンの発現 (2006)
  • Author(s): 山崎学, 丸山智, 程〓, 朔敬
  • Organizer: 第38回日本結合組織学会学術大会
  • Place of Presentation: 前橋市