Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease

Ninjit Dhanota; Amanjit Bal; Gurpreet Singh; Sunil K Arora

Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease

J Clin Transl Res. 2021 Sep 29;7(5):687-700. eCollection 2021 Oct 26.

Authors

Ninjit Dhanota^{1

2}, Amanjit Bal³, Gurpreet Singh⁴, Sunil K Arora¹

Affiliations

¹ Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
² Department of Radiation Oncology, Weill Cornell Medicine, New York, USA.
³ Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
⁴ Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

PMID: 34778599
PMCID: PMC8580523

Abstract

Background and aim: To delineate the underlying molecular mechanisms responsible for the intratumoral enrichment of breast cancer stem cells (BCSCs) in aggressive breast tumors, we evaluated the frequency and characteristics of BCSCs within the tumor tissue in primary human breast carcinomas. We assessed the expression profiles of various genes in cancer cells (CC) and stromal cells (SC) from these tumors to delineate the role played by the cellular niche in de novo origin or expansion of intra-tumoral cancer stem cells (CSC).

Method: The study included primary tumor and adjacent normal breast tissue specimens from chemotherapy-naïve breast carcinoma patients. The BCSCs, identified as Lin^-CD44⁺CD24^- and aldehyde dehydrogenase 1 A1 positive, were enumerated. The flow-cytometrically sorted stromal, and CC were processed for gene expression profiling using a custom-designed polymerase chain reaction array of genes known to facilitate disease progression.

Results: The frequency of BCSCs within the tumor mass correlated significantly with histopathological and molecular grades of tumors, indicating a direct relationship of BCSC with the aggressive behavior of breast cancer. Further, a significantly increased expression of the genes associated with growth factors, cytokines and matricellular proteins in tumors were found in high BCSCs compared to Lo-BCSC tumors, suggesting the possible contribution of stromal and CC in an intratumoral expansion of CSCs. Similarly, a significant upregulation of genes associated with hypoxia and angiogenesis in Hi-BCSCs tumors further supported the role of a hypoxic environment.

Conclusion: Overall, the findings suggest the molecular crosstalk between SC and CC potentially (directly or indirectly) contributes to the expansion of CSC.

Relevance for patients: The current study highlights the importance of CSC as a potential future predictive/prognostic marker for aggressive breast cancer. The present study predicts the potential risk stratification based on the frequency of BCSCs in primary breast tumors and existing prognostic factors.

Keywords: breast cancer stem cell; epithelial to mesenchymal transition; extracellular matrix; metastatic tumors; primary human breast cancer; tumor microenvironment.