Molecular heterogeneity in breast carcinoma cells with increased invasive capacities

  • Giulia Negro

Abstract

Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. Cancer cell spreading can only be executed if the cells possess increased invasive abilities to pass a number of biological barriers to reach a target organ. Although carcinoma cells of different breast cancer subtypes should conquer the same spreading roads, it is unclear whether they exploit any common molecular pathways to maintain their invasive and metastatic capabilities. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. It was found that newly obtained INV cells have demonstrated very similar morphology which is specific for carcinoma cells possessing the augmented invasive and migratory capacities. As it was expected, all three INV cells belonging to different subtypes of breast cancer also showed enhanced migratory and invasive abilities. However, the metastasis-related molecular properties of the investigated INV cells were distinctly affected in the cells of different breast cancer subtypes. The global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Thus, MDA-MB-231-INV and T47D-INV had 365 equally up- and down-regulated proteins, whereas Au565-INV cells had an overlapping with MDA-MB-231-INV and T47D-INV in 74 and 39 deregulated proteins, respectively. Comparable situation was observed with the deregulated pathways in the investigated INV cells. Invasive MDA-MB-231-INV and T47D-INV had an overlap of 223 up- and down-regulated pathways, whereas MDA-MB-231-INV and Au565-INV cells had only 35 overlapping pathways; and T47D-INV and Au565-INV cells possessed 22 commonly regulated pathways. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers.

Published
2020-03-25
How to Cite
Negro, G. (2020). Molecular heterogeneity in breast carcinoma cells with increased invasive capacities. Radiology and Oncology, 54(1), 103-118. Retrieved from https://radioloncol.com/index.php/ro/article/view/3391
Section
Clinical oncology