Browsing by Subject "LGR5"

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    Comparable expression of stem markers and damage-responsive proteins in untreated and chemoradiation-treated rectal cancer
    (2026) Sachi Sekine; Hirotoshi Kawata; Tomoko Kamiakito; Takeo Nakaya; Yasuyuki Miyakura; Koichi Suzuki; Toshiki Rikiyama; Akira Tanaka1; Kentaro Tsuji; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
    Purpose. Cancer stem cells (CSCs) are suggested to contribute to therapy resistance in rectal cancer. However, histopathological analysis of CSCs is still lacking in rectal cancer. Methods. The expression of leucine-rich, repeat containing G protein-coupled receptor 5 (LGR5), proto oncogene, polycomb ring finger 1 (BMI1), yes associated transcriptional regulator (YAP) and its paralog TAZ (hereafter, YAP/TAZ), and nuclear β catenin was compared in untreated and chemoradiation treated (CRT) rectal cancer by in situ hybridization and immunostaining. Niche factors were also compared in human rectal cancer specimens and the embryonic intestine. Results. The mean ratios were 15% and 14% for LGR5, 30% and 33% for BMI1, 2.7% and 7.6% for YAP/TAZ, and 38% and 32% for nuclear β-catenin in untreated and CRT rectal cancer, respectively, showing no significant differences for these stem markers following CRT. The stromal expression ratios of YAP/TAZ were 9.7% and 23% in untreated and CRT rectal cancer, which indicated significant upregulation and confirmation of the damage response in the stroma of CRT tumors. In addition, cancer cells co-expressing LGR5 and CDKN1B are also comparable in untreated and CRT rectal cancer. For niche factors, we found that WNT2B and GREM1 were uniformly expressed in rectal cancer with a pattern similar to that of the early embryonic intestine. Conclusion. The expression of LGR5, BMI1, CDKN1B, and YAP/TAZ was comparable in untreated and CRT rectal cancer. The uniform expression of mesenchymal niche factors might prevent the zonation of the stem cell niche in rectal cancer
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    Protruding structures with high expression of LGR5 are formed during regrowth phase after chemo-treatment in xenograft model of colorectal adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Yamazaki, Masaki; Kato, Atsuhiko; Sawada, Noriaki; Watanabe, Takeshi; Suzuki, Masami
    Recurrence after chemotherapy is one of the biggest obstacles in cancer therapy, along with metastasis. Although histopathological evaluation in preclinical models like the xenograft model help us to understand the pathophysiological process of tumor growth, there are not enough detailed histopathological analyses of such models. In this study, to learn how a tumor recovers the typical tumor structure after structural corruption during chemo-treatment, xenografted tumors originating from a patient-derived xenograft of colorectal cancer (CRC) were analyzed histopathologically over time. There were many Duct (Flattened) at Day 1 (one day after the final administration of Irinotecan), but the ratio of Duct (Columnar) and Cribriform—structures typically found in colorectal adenocarcinoma—increased over time. Finally, at Day 15 (15 days after the final administration of Irinotecan), tumor structure and size were once again the same as in the control group. LGR5, a known cancer stem cell (CSC) marker for CRC, was highly expressed on protruding structures observed from Duct (Flattened) during their transformation into Duct (Columnar) and Cribriform. In addition, these LGR5-expressing protruding structures were either Ki67 negative or positive. These results suggest that the formation of protruding structures on Duct (Flattened) is a pivotal first step in the regrowth of tumors