Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition.
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.
Université de Reims Champagne Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.|Biochemistry, Biochemical Analysis &Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.|CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France.
Konstantina
K
Karamanou
Department for Life Quality Studies, University of Bologna, Rimini, Italy.
Marco
M
Franchi
Biochemistry, Biochemical Analysis &Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
Zoi
Z
Piperigkou
Université de Reims Champagne Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.|CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France.
Corinne
C
Perreau
Université de Reims Champagne Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.|CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
Francois-Xavier
FX
Maquart
Biochemistry, Biochemical Analysis &Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
Demitrios H
DH
Vynios
Université de Reims Champagne Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.|CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France.
Stéphane
S
Brézillon
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006801:Humans; D000071234:Lumican / Q000494:pharmacology*; D061986:MCF-7 Cells; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*
D000071234:Lumican; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D019859:Proto-Oncogene Proteins c-met