Abstract
Adipose tissue is no longer considered to be solely an energy storage, but exerts important endocrine functions, which are primarily mediated by a network of various soluble factors derived from fat cells, called adipocytokines. In addition to their responsibility to influence energy homeostasis, new studies have identified important pathways linking metabolism with the immune system, and demonstrating a modulatory role of adipocytokines in immune function. Additionally, epidemiological studies underline that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Whereas a possible influence of adipocytokines on the proliferation of tumor cells is already known, new evidence has come to light elucidating a modulatory role of this signaling substances in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is a key feature to fight cancer cells, whereas the locomotion of tumor cells is a prerequisite for tumor formation and metastasis. We herein review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of adipocytokines in the regulation of migration of both leukocytes and tumor cells, and gives an insight in the underlying molecular mechanisms.
Highlights
The prevalence and incidence of obesity and obesityrelated diseases has increased dramatically over the past decades
We review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis
Adiponectin and leptin are the most abundant adipocytokines produced by adipocytes, and the best-studied molecules in this class so far
Summary
The prevalence and incidence of obesity and obesityrelated diseases has increased dramatically over the past decades. This conclusion is confirmed by results which demonstrate an influence of leptin on breast cancer development in relation to estrogen receptor status [40], and illuminate the growth-inducing effect of leptin in estrogen receptor-positive breast cancer cells by its stimulation of aromatase expression and the accompanied increase of estrogen levels through the aromatization of androgens [15] All these data clearly support a direct functional role of leptin in processes related to cancer initiation and/or progression by promoting the migration and proliferation of carcinoma cells, resulting in metastatic development. In human endometrial and hepatocellular carcinoma cells leptin was shown to promote proliferation and invasion by rapidly stimulating the JAK/STAT-pathway and inducing the phosphorylation of ERK and AKT, activating these key signal transduction pathways associated with cell growth and cell migration [37,38,42]. An increasing number of studies confirm and improve the existing findings, there is more to be studied to better understand the mechanisms underlying the antiproliferative as well as the pro-migratory effects of adiponectin
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