Abstract
Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology. In this report, we evaluated the effects of lumican in respect to the ERs-associated breast cancer cell behaviour, before and after suppression of ERs, using scanning electron and confocal microscopies, qPCR and functional assays. Our data pinpointed that lumican significantly attenuated cell functional properties, including proliferation, migration and invasion. Furthermore, it modified cell morphology, inducing cell-cell junctions, evoked EMT/MET reprogramming and suppressed the expression of major matrix effectors (matrix metalloproteinases and EGFR) implicated in breast cancer progression. The effects of lumican were found to be related to the type of breast cancer cells and the ERα/β type. These data support the anticancer activity of lumican and open a new area for the pharmacological targeting of the invasive breast cancer.
Highlights
Extracellular matrix (ECM) is a dynamic network of macromolecules contributing to cell behaviour, gene expression and diverse functional properties[7]
Regarding ECM remodelling, lumican is involved in the inhibition of cancer invasion and metastasis, in the suppression of cell proliferation, in the inhibition of angiogenesis and in the inflammatory response[16,17,18,19,20,21,22]
It has been recently demonstrated that the knockdown of ERαin ERα(+) MCF-7 breast cancer cells (MCF-7/SP10+) induced profound morphological changes, including mesenchymal characteristics such as elongated shape, numerous cytoplasmic protrusions and the ability to grow distant to each other (Fig. 1a, image C)
Summary
Extracellular matrix (ECM) is a dynamic network of macromolecules contributing to cell behaviour, gene expression and diverse functional properties[7]. Small leucine-rich PGs (SLRPs) are among the most ubiquitously expressed class in the ECM Their pericellular localization and the substitution of their core protein by one or more highly negative glycosaminoglycan (GAG) chains, enable the interactions of SLRPs with matrix effectors, such as cytokines, growth factors and cell surface receptors. These interactions lead to the modification of fundamental cell functional properties, such as migration, apoptosis, autophagy, angiogenesis, and metastatic potential of cancer cells[12,13,14]. These findings are promising and could be potentially applied for designing novel pharmaceutical agents for breast cancer therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
