Establishment and Molecular Characterization of a Short‐Term Primary Culture Derived From Invasive Micropapillary Carcinoma of the Breast

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Invasive micropapillary carcinoma (IMPC) of the breast, a rare and aggressive subtype, represents a unique morphology of reversed polarity with higher metastatic propensity. Due to the limited availability of experimental models, understanding distinct molecular pathways and potential therapeutic targets remains challenging. This study aimed to establish patient-derived cell cultures (PDCs) from IMPC to generate viable models for in-vitro studies. Tissue samples from five IMPC cases were enzymatically disaggregated using five different cell disaggregation protocols. These cells were characterized using immunofluorescence, short tandem repeats profiling, and real-time assays for tumor marker expression profiles. RNA sequencing was performed and compared with invasive ductal carcinoma, no special type (IDC-NST), to study differential gene expression and cell polarity markers. Two short-term PDCs were successfully established from IMPC samples with an optimized collagenase-based protocol. These cultures showed an immunohistochemical profile consistent with the original tumor tissues and maintained hormone receptor and MUC1 expression status. RNA sequencing of PDCs revealed similar gene expression patterns with matched tumor tissue and revealed upregulated RAP1, MAPK, and PI3K-AKT pathways, when compared with ER/PR-matched IDC. These PDCs also showed different gene expression patterns in cell-polarity associated genes, such as cadherins CDH2, tight junction gene MARVELD2, PAR complex gene PARD6B, and downregulation of the cell polarity CRB2 gene. This study indicated the need for an optimization of cell culture conditions and the feasibility of establishing patient-derived cell cultures from IMPC. These models provide a great tool to study molecular insights, cell polarity, and therapeutic research in a rare breast cancer subtype.

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