Niche microenvironments are essential for maintaining the phenotypic heterogeneity of primary cancer

ABSTRACT: Cancer is among the major causes of death worldwide, and treatment can be individualized according to a patient’s genotype. Primary cultures of cancer and normal cells provide more accurate information about tumour pathology compared with tumour-derived cell lines, and several methods are available for establishing primary cultures. However, these methods are inefficient, complicated and expensive. Here we describe a method to establish primary cultures of tumour cells, which we designate “isolated tumour-derived Cancer Cells” (iCCs) that retains the phenotypic heterogeneity of primary cancer cells in their in situ niche microenvironments. We used a custom filter, a Matrigel-coated plate, and modified embryonic stem cell (ESC) culture medium to isolate iCCs from tumour tissues of patients with colorectal cancer. All iCCs were viable, and approximately 90% of the cultures were passaged. The morphologies, genotypes and transcription profiles of iCCs were similar to those of their respective tumours of origin. Further, iCCs comprised a specific cell population that expressed Platelet-derived growth factor receptor (PDGFR), which contributes to forming the structure of the original ductal carcinoma. Our results demonstrate that ESC culture medium maintained the heterogeneity of ICCs by supporting the viability of PDGFR-expressing cells. The responses of iCCs to standard anti-cancer drugs differed compared with those of colon cancer cell lines. Moreover, the drug sensitivities of iCCs closely correlated with patients’ clinical outcomes. For example, a clinically significant finding was the reduction of the IC50 of crenolanib, an inhibitor of PDGFR signalling, for iCCs. Therefore, crenolanib may serve as an effective chemotherapeutic agent for managing colorectal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99158 | GEO | 2017/05/23

SECONDARY ACCESSION(S): PRJNA387444

REPOSITORIES: GEO