Abstract
Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45-CD34 +CD31+CD13-CCRL2+ endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45-CD34 +CD31-CD13+CD140b+ mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 5880-5891 |
| Number of pages | 12 |
| Journal | Cancer Research |
| Volume | 73 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2013 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer. / Orecchioni, Stefania; Gregato, Giuliana; Martin-Padura, Ines; Reggiani, Francesca; Braidotti, Paola; Mancuso, Patrizia; Calleri, Angelica; Quarna, Jessica; Marighetti, Paola; Aldeni, Chiara; Pruneri, Giancarlo; Martella, Stefano; Manconi, Andrea; Petit, Jean Yves; Rietjens, Mario; Bertolini, Francesco.
In: Cancer Research, Vol. 73, No. 19, 01.10.2013, p. 5880-5891.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer
AU - Orecchioni, Stefania
AU - Gregato, Giuliana
AU - Martin-Padura, Ines
AU - Reggiani, Francesca
AU - Braidotti, Paola
AU - Mancuso, Patrizia
AU - Calleri, Angelica
AU - Quarna, Jessica
AU - Marighetti, Paola
AU - Aldeni, Chiara
AU - Pruneri, Giancarlo
AU - Martella, Stefano
AU - Manconi, Andrea
AU - Petit, Jean Yves
AU - Rietjens, Mario
AU - Bertolini, Francesco
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45-CD34 +CD31+CD13-CCRL2+ endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45-CD34 +CD31-CD13+CD140b+ mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.
AB - Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45-CD34 +CD31+CD13-CCRL2+ endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45-CD34 +CD31-CD13+CD140b+ mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=84885079977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885079977&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-0821
DO - 10.1158/0008-5472.CAN-13-0821
M3 - Article
C2 - 23918796
AN - SCOPUS:84885079977
VL - 73
SP - 5880
EP - 5891
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 19
ER -