Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   department of obstetrics and gynecology   助教  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Pathological classification of desmoplastic reaction is prognostic factor in cervical adenocarcinoma.

  Taishi Akimoto, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Motoki Matsuura, Masato Tamate, Masahiro Iwasaki, Shutaro Habata, Taro Murakami, Makoto Osanai, Tsuyoshi Saito

  Medical molecular morphology   55 ( 4 ) 275 - 282  2022.07  [Domestic journal]

  　View Summary

  Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.

  DOI PubMed

• Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

  Yui Ito, Akira Takasawa, Kumi Takasawa, Taro Murakami, Taishi Akimoto, Daisuke Kyuno, Yuka Kawata, Kodai Shano, Kurara Kirisawa, Misaki Ota, Tomoyuki Aoyama, Masaki Murata, Kotaro Sugimoto, Hideki Chiba, Tsuyoshi Saito, Makoto Osanai

  Cancer science   113 ( 4 ) 1519 - 1530  2022.04  [International journal]

  　View Summary

  Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin-6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma (ADC) and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell-cell adhesion-related proteins and drug metabolism-associated proteins (aldo-keto reductase [AKR] family proteins) were significantly increased in CLDN6-overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell-cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical ADC, possibly due to increased cell-cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6-targeting therapy, against cervical ADC.

  DOI PubMed

• Regulatory roles of claudin-1 in cell adhesion and microvilli formation.

  Kumi Takasawa, Akira Takasawa, Taishi Akimoto, Kazufumi Magara, Tomoyuki Aoyama, Hiroshi Kitajima, Taro Murakami, Yusuke Ono, Daisuke Kyuno, Hiromu Suzuki, Makoto Osanai

  Biochemical and biophysical research communications   565   36 - 42  2021.08  [International journal]

  　View Summary

  Aberrant expression of tight junction proteins has recently been focused on in the cancer research field. We previously showed that claudin-1 is aberrantly expressed from an early stage of uterine cervical adenocarcinoma and contributes to malignant potentials. To elucidate the molecular mechanisms underlying tumor-promoting roles of claudin-1, we established and analyzed claudin-1 knockout cells. Knockout of claudin-1 suppressed conventional tight junctional functions, barrier and fence functions, and expression of cell adhesion-associated proteins including E-cadherin. Comparative proteome analysis revealed that expression of claudin-1 affected expression of a wide range of proteins, especially proteins that are associated with cell adhesion and actin cytoskeleton remodeling. Interactome analysis of the identified proteins revealed that E-cadherin and focal adhesion kinase play central roles in the claudin-1-dependently affected protein network. Moreover, knockout of claudin-1 significantly suppressed microvilli formation and activity of Ezrin/Radixin/Moesin. Taken together, the results indicate that expression of claudin-1 affects not only conventional tight junction function but also expression and activity of a wide range of proteins, especially proteins that are associated with cell adhesion and actin cytoskeleton remodeling, to contribute to malignant potentials and microvilli formation in cervical adenocarcinoma cells.

  DOI PubMed

• Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.

  Taro Murakami, Akira Takasawa, Kumi Takasawa, Taishi Akimoto, Tomoyuki Aoyama, Kazufumi Magara, Yuki Saito, Misaki Ota, Daisuke Kyuno, Soh Yamamoto, Tadashi Hasegawa, Tsuyoshi Saito, Makoto Osanai

  Cancer science   112 ( 2 ) 906 - 917  2021.02  [International journal]

  　View Summary

  Recent studies have shown that aberrant expression of tight junction proteins (TJP) contributes to malignant potential of various cancers. In the present study, we investigated the expression of junctional adhesion molecule-A (JAM-A), one of the transmembrane TJP, in uterine cervical adenocarcinoma and the significance of its expression for malignancy. Immunohistochemistry on human surgical specimens showed that JAM-A was aberrantly expressed in neoplastic regions including adenocarcinoma in situ (AIS). Knockout of JAM-A significantly suppressed cell proliferation and colony-forming and migration abilities. We also showed that an antibody specific to an extracellular region of JAM-A reduced cell proliferation ability and that loss of JAM-A increased drug sensitivity of cervical adenocarcinoma cells. Based on a comprehensive proteome analysis, we found that poliovirus receptor (PVR/CD155) was regulated by JAM-A and formed a physical interaction with JAM-A. In human surgical specimens, PVR/CD155 expression was significantly correlated with some clinicopathological features and prognosis of cervical adenocarcinoma. Interestingly, most of the PVR/CD155-positive cases expressed a high level of JAM-A, and patients with the expression pattern of PVR/CD155 positive/JAM-A high had significantly shorter periods of relapse-free survival (P = .00964) and overall survival (P = .0204) than those for the other patients. Our observations suggest that aberrant expression of JAM-A promotes malignancy of uterine cervical adenocarcinoma by regulation of PVR/CD155, and JAM-A is therefore a potential therapeutic target for this malignancy.

  DOI PubMed

• A Case of Endometrial Carcinosarcoma Containing Sertoliform Endometrioid Carcinoma Component.

  Satoru Munakata, Hanae Kushibiki, Taishi Akimoto, Tsuyoshi Yamashita, Norihiko Shimoyama

  Case reports in pathology   2021   5868818 - 5868818  2021  [International journal]

  　View Summary

  Carcinosarcomas (CSs) of the endometrium have admixture of malignant epithelial and mesenchymal components. The carcinomatous component exhibit endometrioid, serous, or clear cell differentiation, or are undifferentiated. CSs are considered homologous or heterologous according to the type of sarcomatous component. Sertoliform endometrioid carcinomas (SECs) of the endometrium which comprise a rare subtype of endometrial cancer, typically occur in the ovary. SECs as a carcinomatous component of CS of the endometrium have not been reported. Here, we report an endometrial carcinosarcoma that contains an SEC component. An 88-year-old female presented to a clinic with atypical genital bleeding. She was referred to our hospital and underwent total hysterectomy, bilateral adnexectomy and partial omentectomy due to endometrial carcinoma. Gross examination revealed a polypoid mass in the uterine cavity with massive myometrial invasion. Histologically, the tumor was a high-grade endometrioid carcinoma. In addition to an ordinary conventional endometrioid carcinoma, approximately 30% of the area exhibited sex cord-like pattern and contained small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Immunohistochemically, the SEC component showed diffuse p53 staining. Sex cord-like area, especially the solid area, showed positive staining for EMA, vimentin, α-inhibin, CD99, calretinin, p53, CD56, synaptophysin, and chromogranin A, which is a staining pattern similar to that previously reported SEC of the endometrium. Diminished membranous and positive cytoplasmic staining for β-catenin was observed. This is the first case report of an endometrial carcinosarcoma containing an SEC component. SECs of the endometrium might exhibit sex cord-like differentiation in contrast to SECs of the ovary, which do not exhibit sex cord differentiation.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 平滑筋肉腫のFFPE組織標本を用いた新規バイオマーカー探索の試み

  高澤 啓, 伊野 善彦, 青山 智志, 秋元 太志, 中西 敬太郎, 村田 雅樹, 小山内 誠, 長谷川 匡, 澤田 典均

  日本病理学会会誌 ( (一社)日本病理学会 )  106 ( 1 ) 288 - 288  2017.03

• 平滑筋肉腫のFFPE組織標本を用いた新規バイオマーカー探索の試み

  中西 敬太郎, 高澤 啓, 青山 智志, 上田 朝子, 秋元 太志, 村田 雅樹, 田中 敏, 小山内 誠, 長谷川 匡, 澤田 典均

  日本病理学会会誌 ( (一社)日本病理学会 )  105 ( 1 ) 602 - 602  2016.04

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Proteomic analysis of placental FFPE tissue to elucidate the pathogenesis of early-onset pre-eclampsia and its clinical application.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2024.04

  -

  2027.03

   

  染谷 真行, 高澤 啓, 秋元 太志

• エストロゲンが寄与するがん微小環境を含めた子宮頸部腺がんの新たな悪性化機序の解明

  若手研究

  Project Year :

  2022.04

  -

  2025.03

   

  秋元 太志

• Redefining cervical adenocarcinoma as estrogen-dependent cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

  -

  2023.03

   

  高澤 啓, 秋元 太志, 青山 智志

  　View Summary

  子宮頸部腺がん(以下、頸部腺がん)は核内エストロゲン受容体(ER)が陰性であることから、エストロゲン非依存性がんとして理解されてきた。我々は、頸部腺がんの手術材料および細胞株で膜型エストロゲン受容体GPR30が高発現し、エストロゲン依存性にタイト結合蛋白質 claudin-1発現を調節して悪性化に関与していることなどを明らかにした(Akimoto et al. Neoplasia, 2018)。本研究では、GPR30を軸にエストロゲンが寄与する悪性化メカニズムを明らかにし、頸部腺がんをエストロゲン依存性がんとして再定義し、新たな治療戦略策定へつなげることを目的とする。その達成のため、頸部腺がんにおいて①エストロゲン関連刺激が腫瘍に及ぼす効果、②多層オミクス解析によりエストロゲン関連刺激の分子メカニズム、③ヒトパピローマウイルス(HPV)感染とGPR30の関連、を明らかにする これまでに、頸部腺癌手術材料を用いた免疫組織化学的検討を行った。頸部腺癌の手術症例に対し、GPR30、ER、p16、EPV E6、HPV E7の免疫染色を行い、陽性強度・面積を評価しスコア化した。HPV E7については、良好な染色性が得られなかったため、以降の検討は行っていない。病理組織学的因子との関連を解析したところ、T因子や病期とGPR30発現との間に有意な関連があった。ERの発現と予後との有意な相関は得られなかった。これらの結果はまとめて論文として報告している。p16、HPV E6の免疫組織化学の結果は、現在評価中である。平行して、頸部腺がん細胞株にエストロゲン、GPR30作動薬を暴露し、それらの細胞で比較プロテオーム解析を行った。エストロゲン、GPR30作動薬で共通して増加するタンパク質を複数同定した。

• Changes of tight junctions induced by extracellular stimuli determine cell shape and fate.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2016.04

  -

  2019.03

   

  SAWADA NORIMASA, TAKASAWA KUMI, AKIMOTO TAISHI

  　View Summary

  The tight junction (TJ) is an intercellular junction that works as a barrier to external stimulation and as a fence to maintain cell polarity. Recently, aberrant expression of TJ proteins have been reported in various diseases. In this study, we focused mainly on aberrant expression in human tumor and clarified the following. TJ proteins could be diagnostic markers for some tumors including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, lung adenocarcinoma, cervical adenocarcinoma and salivary gland tumors. These findings suggested that TJ proteins are promising targets of cancer therapy. Furthermore, the expression of TJ proteins were involved in the enhancement of the malignancy of carcinoma such as invasion and proliferation. These findings suggested that abnormality of TJ might be involved in tumorigenesis.