Isolation and Characterization of a Novel Mammary Adenocarcinoma, MCa-P1362, with Hormone Receptor Expression, Human Epidermal Growth Factor Receptor 2 Positivity, and Enrichment in Cancer and Mesenchymal Stem Cells

IF 4.7 2区医学 Q1 PATHOLOGY American Journal of Pathology Pub Date : 2024-05-13 DOI:10.1016/j.ajpath.2024.02.013

Samir Jana , Wende Li , Pin-Ji Lei , Zixiong Wang , Shaye Kibara , Peigen Huang , Dennis Jones

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Abstract

Preclinical models that display spontaneous metastasis are necessary to improve the therapeutic options for hormone receptor–positive breast cancers. Within this study, detailed cellular and molecular characterization was conducted on MCa-P1362, a newly established mouse model of metastatic breast cancer that is syngeneic in BALB/c mice. MCa-P1362 cancer cells express estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2. MCa-P1362 cancer cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for growth and tumor progression. Analysis of MCa-P1362 tumor explants revealed the tumors contained a mixture of cancer cells and mesenchymal stromal cells. Through transcriptomic and functional analyses of both cancer and stromal cells, stem cells were detected within both populations. Functional studies demonstrated that MCa-P1362 cancer stem cells drove tumor initiation, whereas stromal cells from these tumors contributed to drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of breast tumor progression and therapeutic resistance.

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具有激素受体表达、人类表皮生长因子受体 2 阳性以及富含癌细胞和间充质干细胞的新型乳腺腺癌 MCa-P1362 的分离与特征描述

要改进激素受体阳性乳腺癌的治疗方案，就必须建立能显示自发性转移的临床前模型。本研究对 MCa-P1362 进行了详细的细胞和分子特性分析，MCa-P1362 是一种新近建立的转移性乳腺癌小鼠模型，可与 BALB/c 小鼠共生。MCa-P1362 癌细胞表达雌激素受体、孕酮受体和人类表皮生长因子受体 2。MCa-P1362 癌细胞在体外和体内对雌激素有增殖反应，但其生长和肿瘤进展并不依赖于类固醇激素。对 MCa-P1362 肿瘤外植体的分析表明，肿瘤含有癌细胞和间质基质细胞的混合物。通过对癌细胞和基质细胞进行转录组学和功能分析，在两种细胞群中都检测到了干细胞。功能研究表明，MCa-P1362癌干细胞驱动了肿瘤的发生，而这些肿瘤的基质细胞则导致了耐药性。MCa-P1362可作为一种有用的临床前模型，用于研究乳腺肿瘤进展和耐药性的细胞和分子基础。

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来源期刊

American Journal of Pathology 医学-病理学

CiteScore

11.40

自引率

0.00%

发文量

178

审稿时长

30 days

期刊介绍： The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.