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Adipocytes and Obes...
Adipocytes and Obesity-Related Conditions Jointly Promote Breast Cancer Cell Growth and Motility : Associations With CAP1 for Prognosis
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- Rosendahl, Ann H (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast cancer prevention & intervention,Lund University Research Groups,Skåne University Hospital
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- Bergqvist, Malin (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast cancer prevention & intervention,Lund University Research Groups,Skåne University Hospital
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- Lettiero, Barbara (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Institutionen för kliniska vetenskaper, Lund,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Department of Clinical Sciences, Lund,Breast cancer prevention & intervention,Lund University Research Groups,Skåne University Hospital
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- Kimbung, Siker (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Institutionen för kliniska vetenskaper, Lund,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Department of Clinical Sciences, Lund,Breast cancer prevention & intervention,Lund University Research Groups,Skåne University Hospital
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- Borgquist, Signe (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Institutionen för kliniska vetenskaper, Lund,Bröstcancer - prevention & intervention,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Department of Clinical Sciences, Lund,Breast cancer prevention & intervention,Lund University Research Groups,Aarhus University Hospital,Aarhus University,Skåne University Hospital
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(creator_code:org_t)
- 2018-11-22
- 2018
- Engelska.
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.frontier...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- The global increase in overweight and obesity rates represent pressing public health concerns associated with severe comorbidities, amongst a rising incidence and impaired outcome of breast cancer. Yet, biological explanations for how obesity affects breast cancer are incompletely mapped. Herein, the joint impact by differentiated 3T3-L1 adipocytes and obesity-related metabolic conditions on breast cancer cells was evaluated in vitro and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines (n = 47) and primary breast tumors (n = 1,881), where associations with survival outcomes were investigated. Adipocytes and metabolic complications jointly stimulated breast cancer cell proliferation and motility, with phenotype-specific differences. Resistin was among the top modulated adipokines secreted by 3T3-L1 adipocytes under obesity-associated metabolic conditions compared with normal physiology. The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast tumors. CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors (P = 0.025), and higher histological grades (P = 0.016). High CAP1 tumor expression was associated with shorter overall survival (adjusted hazard ratio [HRadj] 1.54; 95% confidence interval [CI], 1.11-2.13) and relapse-free survival (HRadj 1.47; 95% CI, 1.10-1.96), compared with low or intermediate CAP1 expression, particularly among ER-positive tumors or lymph node positive tumors. Together, these translational data demonstrate that the adipocyte secretome promote breast cancer cell proliferation and motility and highlight a potential role of CAP1 regarding breast cancer outcome-results that warrant further investigation to elucidate the obesity-breast cancer link in human pathology.
- The global increase in overweight and obesity rates represent pressing public health concerns associated with severe comorbidities, amongst a rising incidence and impaired outcome of breast cancer. Yet, biological explanations for how obesity affects breast cancer are incompletely mapped. Herein, the joint impact by differentiated 3T3-L1 adipocytes and obesity-related metabolic conditions on breast cancer cells was evaluated in vitro and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines (n = 47) and primary breast tumors (n = 1,881), where associations with survival outcomes were investigated. Adipocytes and metabolic complications jointly stimulated breast cancer cell proliferation and motility, with phenotype-specific differences. Resistin was among the top modulated adipokines secreted by 3T3-L1 adipocytes under obesity-associated metabolic conditions compared with normal physiology. The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast tumors. CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors (P = 0.025), and higher histological grades (P = 0.016). High CAP1 tumor expression was associated with shorter overall survival (adjusted hazard ratio [HRadj] 1.54; 95% confidence interval [CI], 1.11–2.13) and relapse-free survival (HRadj 1.47; 95% CI, 1.10–1.96), compared with low or intermediate CAP1 expression, particularly among ER-positive tumors or lymph node positive tumors. Together, these translational data demonstrate that the adipocyte secretome promote breast cancer cell proliferation and motility and highlight a potential role of CAP1 regarding breast cancer outcome—results that warrant further investigation to elucidate the obesity-breast cancer link in human pathology.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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