骨膜炎
癌症研究
血管生成
三阴性乳腺癌
乳腺癌
肿瘤进展
医学
癌症
生物
内科学
细胞生物学
细胞外基质
作者
Tatsuya Fujikawa,Fumihiro Sanada,Yoshiaki Taniyama,Katsushi Shibata,Naruto Katsuragi,Nobutaka Koibuchi,Kenji Akazawa,Yuko Kanemoto,Hidehito Kuroyanagi,Kenzo Shimazu,Hiromi Rakugi,Ryuichi Morishita
出处
期刊:Cancers
[MDPI AG]
日期:2021-10-11
卷期号:13 (20): 5072-5072
被引量:5
标识
DOI:10.3390/cancers13205072
摘要
Periostin (Pn) is involved in multiple processes of cancer progression. Previously, we reported that Pn expression is correlated with mesenchymal tumor markers and poor prognosis in triple-negative breast cancer (TNBC). In the TNBC xenograft model, chemotherapy increased expression of a Pn alternative splicing variant (ASV) with exon 21, and administration of the neutralizing antibody against Pn with exon 21 (Pn-21 Ab) overcame chemoresistance with a reduction in the mesenchymal cancer cell fraction. In the present study, the role of Pn ASV with exon 21 in TNBC progression has been addressed. We first established a stable cell line carrying a fluorescence-based splicing reporter. Pn-positive TNBC has higher expression of genes related to tumor-associated macrophage (TAM) recruitment and ECM-receptor interaction than Pn-negative cells. In a xenograft model, only Pn-positive cells initiated tumor formation, and the Pn-21 Ab suppressed tumor cell growth, accompanied by decreased M2 TAM polarization and the number of tumor vessels. These data suggest that cancer cell-derived Pn ASV educates TAMs and regulates angiogenesis, which in turn establishes a microenvironmental niche that is supportive of TNBC.
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