Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.
Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes.



We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment.



hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes.



We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated state than adipocytes from normal microenvironment. This would indicate a loss of normal functions in mature adipocytes (such as energy storage), in support of others that might favor tumor growth.
Laboratory of Proteoglycans Chemistry and Extracellular Matrix, Institute of Biology and Experimental Medicine (IByME), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
Sabrina Johanna
SJ
Fletcher
Laboratory of Proteoglycans Chemistry and Extracellular Matrix, Institute of Biology and Experimental Medicine (IByME), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
Paula Alejandra
PA
Sacca
Gynecological Surgery and Breast Pathology, Oncology Institute "Alexander Fleming", Buenos Aires, Argentina.
Mercedes
M
Pistone-Creydt
Gynecological Surgery and Breast Pathology, Oncology Institute "Alexander Fleming", Buenos Aires, Argentina.
Federico Andrés
FA
Coló
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
María Florencia
MF
Serra
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
Flavia Eliana
FE
Santino
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
Corina Verónica
CV
Sasso
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
Constanza Matilde
CM
Lopez-Fontana
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
Rubén Walter
RW
Carón
Laboratory of Proteoglycans Chemistry and Extracellular Matrix, Institute of Biology and Experimental Medicine (IByME), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.|Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Juan Carlos
JC
Calvo
Laboratory of Proteoglycans Chemistry and Extracellular Matrix, Institute of Biology and Experimental Medicine (IByME), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina. vpistone@mendoza-conicet.gob.ar.|Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina. vpistone@mendoza-conicet.gob.ar.|Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, Av. Ruiz Leal w/n, General San Martin Park, Mendoza, CP5500, Argentina. vpistone@mendoza-conicet.gob.ar.
Virginia
V
Pistone-Creydt
D000071097:ADAMTS1 Protein / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D060833:Cellular Microenvironment; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D061986:MCF-7 Cells; D054419:Receptors, Adiponectin / Q000378:metabolism; D053675:Versicans / Q000378:metabolism
C475418:ADIPOR1 protein, human; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D017077:Culture Media, Conditioned; D018960:Hyaluronan Receptors; D054419:Receptors, Adiponectin; C508322:VCAN protein, human; D053675:Versicans; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human
Breast cancer; Breast epithelial cells; Epithelial-stromal interactions; Human breast adipose tissue