A large body of evidences has contributed to establish a strict association between adipose tissue and cancer in the contest of metabolic disorders such as obesity. Epidemiological studies have shown that obese patients have a drastically higher risk to develop cancer. This tumor-promoting role in the context of obesity is thought to rely mainly on the aberrant systemic and paracrine release of pro-inflammatory cytokines by fat cells, which ultimately cooperate to boost cancer cell proliferation and metastatic dissemination. In addition, cancer associated adipocytes (CAAs) may contribute in tumor progression by providing a metabolic support to the aberrant bioenergetics demand of cancer cells. However, it still remains to be established whether a relevant pro-inflammatory effect might be exerted by peritumoral adipose tissue in non-obese patients with gastrointestinal cancer. Gastrointestinal cancers are responsible for more deaths than any other cancer in the body. As for other types of cancer, many studies have revealed the strong relationship between gastrointestinal neoplasms and systemic disorders of adipose tissue, such as obesity and diabetes, but almost nothing is known about the local interaction between gastrointestinal cancer cells and peritumoral adipocytes in non-obese/non-diabetic patients. In order to start bridge this gap we assess whether adipose tissue surrounding human gastrointestinal tumors might be altered in terms of adipocyte morphology and inflammatory infiltration. Specifically we compare peritumoral and non-peritumoral adipose tissue (visceral fat distant from tumor lesion) for the adipocyte size and morphology, cell count of lymphocytes (CD3 positive cells, CD3+) and macrophages (CD68 positive cells, CD68+). We found that peritumoral adipose tissue exhibit significantly reduced adipocyte size and increased number of activated lymphocytes and macrophages. Our results provide clinical evidences in support of the emerging notion that adipocytes at the tumor-stroma interface participate in a highly complex vicious cycle organized by cancer cells to promote tumor progression. Specifically our results suggest that peritumoral adipocytes might provide a significant contribution to enhance tumor burden by fueling cancer cell's metabolic demands and providing mitogenic signals via the paracrine release of pro-inflammatory cytokines.
Characterization of cancer - associated adipose tissue.
CHAKIR, Asmaa
2017-01-01
Abstract
A large body of evidences has contributed to establish a strict association between adipose tissue and cancer in the contest of metabolic disorders such as obesity. Epidemiological studies have shown that obese patients have a drastically higher risk to develop cancer. This tumor-promoting role in the context of obesity is thought to rely mainly on the aberrant systemic and paracrine release of pro-inflammatory cytokines by fat cells, which ultimately cooperate to boost cancer cell proliferation and metastatic dissemination. In addition, cancer associated adipocytes (CAAs) may contribute in tumor progression by providing a metabolic support to the aberrant bioenergetics demand of cancer cells. However, it still remains to be established whether a relevant pro-inflammatory effect might be exerted by peritumoral adipose tissue in non-obese patients with gastrointestinal cancer. Gastrointestinal cancers are responsible for more deaths than any other cancer in the body. As for other types of cancer, many studies have revealed the strong relationship between gastrointestinal neoplasms and systemic disorders of adipose tissue, such as obesity and diabetes, but almost nothing is known about the local interaction between gastrointestinal cancer cells and peritumoral adipocytes in non-obese/non-diabetic patients. In order to start bridge this gap we assess whether adipose tissue surrounding human gastrointestinal tumors might be altered in terms of adipocyte morphology and inflammatory infiltration. Specifically we compare peritumoral and non-peritumoral adipose tissue (visceral fat distant from tumor lesion) for the adipocyte size and morphology, cell count of lymphocytes (CD3 positive cells, CD3+) and macrophages (CD68 positive cells, CD68+). We found that peritumoral adipose tissue exhibit significantly reduced adipocyte size and increased number of activated lymphocytes and macrophages. Our results provide clinical evidences in support of the emerging notion that adipocytes at the tumor-stroma interface participate in a highly complex vicious cycle organized by cancer cells to promote tumor progression. Specifically our results suggest that peritumoral adipocytes might provide a significant contribution to enhance tumor burden by fueling cancer cell's metabolic demands and providing mitogenic signals via the paracrine release of pro-inflammatory cytokines.File | Dimensione | Formato | |
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Doctoral thesis_ Characterization of cancer-associated adipose tissue.pdf
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