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Erschienen in: Clinical and Translational Oncology 2/2013

01.02.2013 | Research Article

Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells

verfasst von: Virginia Pistone Creydt, Sabrina Johanna Fletcher, Jimena Giudice, Ariana Bruzzone, Norma Alejandra Chasseing, Eduardo Gustavo Gonzalez, Paula Alejandra Sacca, Juan Carlos Calvo

Erschienen in: Clinical and Translational Oncology | Ausgabe 2/2013

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Abstract

Introduction

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines.

Materials and methods

Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey′s post hoc tests were performed.

Results

Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs.

Conclusions

We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.
Literatur
1.
Zurück zum Zitat Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol 6:715–725PubMedCrossRef Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol 6:715–725PubMedCrossRef
2.
Zurück zum Zitat Iyengar P, Espina V, Williams TW, Lin Y, Berry D, Jelicks LA, Lee H, Temple K, Graves R, Pollard J, Chopra N, Russell RG, Sasisekharan R, Trock BJ, Lippman M, Calvert VS, Petricoin EF 3rd, Liotta L, Dadachova E, Pestell RG, Lisanti MP, Bonaldo P, Scherer PE (2005) Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J Clin Invest 115:1163–1176PubMed Iyengar P, Espina V, Williams TW, Lin Y, Berry D, Jelicks LA, Lee H, Temple K, Graves R, Pollard J, Chopra N, Russell RG, Sasisekharan R, Trock BJ, Lippman M, Calvert VS, Petricoin EF 3rd, Liotta L, Dadachova E, Pestell RG, Lisanti MP, Bonaldo P, Scherer PE (2005) Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J Clin Invest 115:1163–1176PubMed
3.
Zurück zum Zitat Krause S, Maffini MV, Soto AM, Sonnenschein C (2010) The microenvironment determines the breast cancer cells’ phenotype: organization of MCF7 cells in 3D cultures. BMC Cancer 10:263–275PubMedCrossRef Krause S, Maffini MV, Soto AM, Sonnenschein C (2010) The microenvironment determines the breast cancer cells’ phenotype: organization of MCF7 cells in 3D cultures. BMC Cancer 10:263–275PubMedCrossRef
4.
Zurück zum Zitat Wu Y, Kim JY, Zhou S, Smas CM (2008) Differential screening identifies transcripts with depot-dependent expression in white adipose tissues. BMC Genomics 9:397PubMedCrossRef Wu Y, Kim JY, Zhou S, Smas CM (2008) Differential screening identifies transcripts with depot-dependent expression in white adipose tissues. BMC Genomics 9:397PubMedCrossRef
5.
Zurück zum Zitat Tan J, Buache E, Chenard MP, Dali-Youcef N, Rio MC (2011) Adipocyte is a non-trivial, dynamic partner of breast cancer cells. Int J Dev Biol 55:851–859PubMedCrossRef Tan J, Buache E, Chenard MP, Dali-Youcef N, Rio MC (2011) Adipocyte is a non-trivial, dynamic partner of breast cancer cells. Int J Dev Biol 55:851–859PubMedCrossRef
6.
Zurück zum Zitat Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, Garrido I, Escourrou G, Valet P, Muller C (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 71:2455–2465PubMedCrossRef Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, Garrido I, Escourrou G, Valet P, Muller C (2011) Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 71:2455–2465PubMedCrossRef
7.
Zurück zum Zitat Walter M, Liang S, Ghosh S, Hornsby PJ, Li R (2009) Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 28:2745–2755PubMedCrossRef Walter M, Liang S, Ghosh S, Hornsby PJ, Li R (2009) Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 28:2745–2755PubMedCrossRef
8.
Zurück zum Zitat Rajala MW, Scherer PE (2003) Minireview: the adipocyte–at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765–3773PubMedCrossRef Rajala MW, Scherer PE (2003) Minireview: the adipocyte–at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144:3765–3773PubMedCrossRef
9.
Zurück zum Zitat Vona-Davis L, Rose DP (2007) Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 14:189–206PubMedCrossRef Vona-Davis L, Rose DP (2007) Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 14:189–206PubMedCrossRef
10.
Zurück zum Zitat Razmkhah M, Jaberipour M, Erfani N, Habibagahi M, Talei AR, Ghaderi A (2011) Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cell Immunol 266:116–122PubMedCrossRef Razmkhah M, Jaberipour M, Erfani N, Habibagahi M, Talei AR, Ghaderi A (2011) Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cell Immunol 266:116–122PubMedCrossRef
11.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef
12.
Zurück zum Zitat Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252PubMedCrossRef Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252PubMedCrossRef
13.
Zurück zum Zitat Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174PubMedCrossRef Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174PubMedCrossRef
14.
Zurück zum Zitat Pistone Creydt V, Sacca PA, Tesone AJ, Vidal L, Calvo JC (2010) Adipocyte differentiation influences the proliferation and migration of normal and tumoral breast epithelial cells. Mol Med Report 3:433–439 Pistone Creydt V, Sacca PA, Tesone AJ, Vidal L, Calvo JC (2010) Adipocyte differentiation influences the proliferation and migration of normal and tumoral breast epithelial cells. Mol Med Report 3:433–439
15.
Zurück zum Zitat Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C (2004) The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci 117:1495–1502PubMedCrossRef Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C (2004) The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci 117:1495–1502PubMedCrossRef
16.
Zurück zum Zitat Maffini MV, Calabro JM, Soto AM, Sonnenschein C (2005) Stromal regulation of neoplastic development. Age-dependent normalization of neoplastic mammary cells by mammary stroma. Am J Pathol 167:1405–1410PubMedCrossRef Maffini MV, Calabro JM, Soto AM, Sonnenschein C (2005) Stromal regulation of neoplastic development. Age-dependent normalization of neoplastic mammary cells by mammary stroma. Am J Pathol 167:1405–1410PubMedCrossRef
17.
Zurück zum Zitat Baker SG, Cappuccio A, Potter JD (2010) Research on early-stage carcinogenesis: are we approaching paradigm instability? J Clin Oncol 28:3215–3218PubMedCrossRef Baker SG, Cappuccio A, Potter JD (2010) Research on early-stage carcinogenesis: are we approaching paradigm instability? J Clin Oncol 28:3215–3218PubMedCrossRef
18.
Zurück zum Zitat Zangani D, Darcy KM, Shoemaker S, Ip MM (1999) Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells. Exp Cell Res 247:399–409PubMedCrossRef Zangani D, Darcy KM, Shoemaker S, Ip MM (1999) Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells. Exp Cell Res 247:399–409PubMedCrossRef
19.
Zurück zum Zitat Rahimi N, Saulnier R, Nakamura T, Park M, Elliott B (1994) Role of hepatocyte growth factor in breast cancer: a novel mitogenic factor secreted by adipocytes. DNA Cell Biol 13:1189–1197PubMedCrossRef Rahimi N, Saulnier R, Nakamura T, Park M, Elliott B (1994) Role of hepatocyte growth factor in breast cancer: a novel mitogenic factor secreted by adipocytes. DNA Cell Biol 13:1189–1197PubMedCrossRef
20.
Zurück zum Zitat Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C, Muehlberg F, Beckmann C, Song YH (2009) Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett 284:80–85PubMedCrossRef Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C, Muehlberg F, Beckmann C, Song YH (2009) Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett 284:80–85PubMedCrossRef
21.
Zurück zum Zitat Dirat B, Bochet L, Escourrou G, Valet P, Muller C (2010) Unraveling the obesity and breast cancer links: a role for cancer-associated adipocytes? Endocr Dev 19:45–52PubMedCrossRef Dirat B, Bochet L, Escourrou G, Valet P, Muller C (2010) Unraveling the obesity and breast cancer links: a role for cancer-associated adipocytes? Endocr Dev 19:45–52PubMedCrossRef
22.
Zurück zum Zitat Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N (2008) Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect 116:1642–1647PubMedCrossRef Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N (2008) Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect 116:1642–1647PubMedCrossRef
23.
Zurück zum Zitat Borcherding DC, Hugo ER, Idelman G, De Silva A, Richtand NW, Loftus J, Ben-Jonathan N (2011) Dopamine receptors in human adipocytes: expression and functions. PLoS One 6:e25537PubMedCrossRef Borcherding DC, Hugo ER, Idelman G, De Silva A, Richtand NW, Loftus J, Ben-Jonathan N (2011) Dopamine receptors in human adipocytes: expression and functions. PLoS One 6:e25537PubMedCrossRef
24.
Zurück zum Zitat Al-Lahham S, Roelofsen H, Rezaee F, Weening D, Hoek A, Vonk R, Venema K (2012) Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur J Clin Invest 42:357–364PubMedCrossRef Al-Lahham S, Roelofsen H, Rezaee F, Weening D, Hoek A, Vonk R, Venema K (2012) Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur J Clin Invest 42:357–364PubMedCrossRef
25.
Zurück zum Zitat Vázquez SM, Mladovan A, Garbovesky C, Baldi A, Lüthy IA (2004) Three novel hormone-responsive cell lines derived from primary human breast carcinomas: functional characterization. J Cell Physiol 199:460–469PubMedCrossRef Vázquez SM, Mladovan A, Garbovesky C, Baldi A, Lüthy IA (2004) Three novel hormone-responsive cell lines derived from primary human breast carcinomas: functional characterization. J Cell Physiol 199:460–469PubMedCrossRef
26.
Zurück zum Zitat Bruzzone A, Vanzulli SI, Soldati R, Giulianelli S, Lanari C, Lüthy IA (2009) Novel human breast cancer cell lines IBH-4, IBH-6, and IBH-7 growing in nude mice. J Cell Physiol 219:477–484PubMedCrossRef Bruzzone A, Vanzulli SI, Soldati R, Giulianelli S, Lanari C, Lüthy IA (2009) Novel human breast cancer cell lines IBH-4, IBH-6, and IBH-7 growing in nude mice. J Cell Physiol 219:477–484PubMedCrossRef
27.
Zurück zum Zitat Retta SF, Ternullo M, Tarone G (1999) Adhesion to matrix proteins. In: Dejana E, Corada M (eds) Adhesion protein protocols, Humana Press INC., Totowa pp 125–130 Retta SF, Ternullo M, Tarone G (1999) Adhesion to matrix proteins. In: Dejana E, Corada M (eds) Adhesion protein protocols, Humana Press INC., Totowa pp 125–130
28.
Zurück zum Zitat Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Weaver D, Muss H, Plaut K (2009) Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat 114:47–62PubMedCrossRef Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Weaver D, Muss H, Plaut K (2009) Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat 114:47–62PubMedCrossRef
29.
Zurück zum Zitat Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong JL, Naidu S, Wei G, Sharma SM, Stephens JA, Fernandez SA, Gurcan MN, Weinstein MB, Barsky SH, Yee L, Rosol TJ, Stromberg PC, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC, Leone G (2009) Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 461:1084–1091PubMedCrossRef Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong JL, Naidu S, Wei G, Sharma SM, Stephens JA, Fernandez SA, Gurcan MN, Weinstein MB, Barsky SH, Yee L, Rosol TJ, Stromberg PC, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC, Leone G (2009) Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 461:1084–1091PubMedCrossRef
30.
Zurück zum Zitat Sacca PA, Pistone Creydt V, Tesone AJ, Calvo JC (2009) A novel and alternative in vitro method using microwave to study the epithelial-stromal interactions. Sci Res Essays 4:1487–1495 Sacca PA, Pistone Creydt V, Tesone AJ, Calvo JC (2009) A novel and alternative in vitro method using microwave to study the epithelial-stromal interactions. Sci Res Essays 4:1487–1495
Metadaten
Titel
Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells
verfasst von
Virginia Pistone Creydt
Sabrina Johanna Fletcher
Jimena Giudice
Ariana Bruzzone
Norma Alejandra Chasseing
Eduardo Gustavo Gonzalez
Paula Alejandra Sacca
Juan Carlos Calvo
Publikationsdatum
01.02.2013
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 2/2013
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-012-0896-x

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