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Adiposity and Adipokines: Roles in the Local Spread of Cancer...
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Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 25081

Special Issue Editor

Dr. Paola Maroni

E-Mail Website
Guest Editor
Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi 4, 20161 Milano, Italia
Interests: breast cancer; bone metastasis; tumor microenvironment; invasive growth; epithelial–mesenchymal transition; autophagy; signal transduction; immunohistochemistry; animal models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A highly heterogeneous population of cells in the microenvironment surrounding tumor cells is responsible for a large number of factors that are important for cancer spread and metastasis, highlighting the importance of tumor–microenvironment cross-talk in influencing tumor growth progression. In this context, adipocytes assume a relevant role: They are capable of producing different factors (i.e., adipokines, cytokines, and chemokines); among them, leptin, adiponectin, resistin, autotaxin, and IL-6 are relevant signals arising from tumor stroma, involved in the initiation and progression of cancer. Moreover, many adipokines, through up- or down-regulation of miRNAs, exert oncogenic or anti-tumor effects. In particular, bone marrow adipose tissue (BMAT) is beginning to emerge as an important contributor to cancer progression in bone metastasis. In addition to producing a plethora of adipokines, BMAT releases extracellular vesicles, which may influence cells in the surrounding area. However, the role of adipocytes and adipose tissue in the metastatic microenvironment remains an important issue to be explored: More detailed knowledge of the link(s) between adiposity and cancer development is needed to find new targets to counteract cancer local invasion and metastasis.

This Special Issue aims to collect recent results regarding the link between adiposity and cancer development and spread to local and distant sites, and to focus on the potential of adipokines and their signaling axes as targets in cancer therapy. Original articles and reviews will be considered.

This Special Issue is jointly organized between IJMS and Biomedicines. In accordance with the Aims and Scope of these journals, articles showing basic studies in biochemistry, molecular biology, and molecular medicine can be submitted to IJMS, whereas articles presenting more clinical content can be submitted to Biomedicines.

Dr. Paola Maroni
Guest Editor

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Keywords

  • cancer
  • metastasis
  • tumor microenvironment
  • adipocytes
  • adiposity
  • adipokines
  • obesity
  • bone marrow adipose tissue
  • miRNAs
  • extracellular vesicles
  • therapy

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Published Papers (5 papers)

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Review

28 pages, 1081 KiB  
Review
Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer
by Yetirajam Rajesh and Devanand Sarkar
Int. J. Mol. Sci. 2021, 22(4), 2163; https://doi.org/10.3390/ijms22042163 - 22 Feb 2021
Cited by 42 | Viewed by 5206
Abstract
Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between [...] Read more.
Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC. Full article
(This article belongs to the Special Issue Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development)
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31 pages, 912 KiB  
Review
Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines
by Silvia Perego, Veronica Sansoni, Ewa Ziemann and Giovanni Lombardi
Int. J. Mol. Sci. 2021, 22(4), 2005; https://doi.org/10.3390/ijms22042005 - 18 Feb 2021
Cited by 17 | Viewed by 4392
Abstract
Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations [...] Read more.
Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the adipose-tissue-derived mediators of low-grade chronic inflammation, i.e., adipokines, as well as the adipokine-mediated impacts of physical activity on tumor development, growth, and metastasis. Importantly, exercise training may be effective in mitigating the side effects related to anti-cancer treatment, thereby underlining the importance of encouraging cancer patients to engage in moderate-intensity activities. However, the strong need to customize and adapt exercises to a patient’s abilities is apparent. Besides the preventive effects of physically active behavior against the adipokine-stimulated cancer risk, it remains poorly understood how physical activity, through its actions as an adipokine, can actually influence the onset and development of metastases. Full article
(This article belongs to the Special Issue Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development)
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22 pages, 1282 KiB  
Review
Tumor Metabolic Reprogramming by Adipokines as a Critical Driver of Obesity-Associated Cancer Progression
by Duc-Vinh Pham and Pil-Hoon Park
Int. J. Mol. Sci. 2021, 22(3), 1444; https://doi.org/10.3390/ijms22031444 - 1 Feb 2021
Cited by 37 | Viewed by 5116
Abstract
Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and [...] Read more.
Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and tumor-suppressing properties in an adipokine type- and context-dependent manner. Increasing evidence has indicated that these adipose tissue-derived hormones differentially modulate cancer cell-specific metabolism. Some adipokines, such as leptin, resistin, and visfatin, which are overproduced in obesity and widely implicated in different stages of cancer, promote cellular glucose and lipid metabolism. Conversely, adiponectin, an adipokine possessing potent anti-tumor activities, is linked to a more favorable metabolic phenotype. Adipokines may also play a pivotal role under the reciprocal regulation of metabolic rewiring of cancer cells in tumor microenvironment. Given the fact that metabolic reprogramming is one of the major hallmarks of cancer, understanding the modulatory effects of adipokines on alterations in cancer cell metabolism would provide insight into the crosstalk between obesity, adipokines, and tumorigenesis. In this review, we summarize recent insights into putative roles of adipokines as mediators of cellular metabolic rewiring in obesity-associated tumors, which plays a crucial role in determining the fate of tumor cells. Full article
(This article belongs to the Special Issue Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development)
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21 pages, 1185 KiB  
Review
The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis
by Eunah Shin and Ja Seung Koo
Int. J. Mol. Sci. 2020, 21(14), 4967; https://doi.org/10.3390/ijms21144967 - 14 Jul 2020
Cited by 26 | Viewed by 4958
Abstract
The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted [...] Read more.
The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted by both, are expected to play the most important role. Bone marrow adipocyte (BMA) is one of the cell types comprising the bone, and adipokine is one of the cytokines secreted by both breast cancer cells and BMAs. These BMAs and adipokines are known to be responsible for cancer progression, and this review is focused on how BMAs and adipokines work in the process of breast cancer bone metastasis. Their potential as suppressive targets for bone metastasis is also explored in this review. Full article
(This article belongs to the Special Issue Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development)
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18 pages, 1538 KiB  
Review
Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer
by Paola Maroni
Int. J. Mol. Sci. 2020, 21(3), 1051; https://doi.org/10.3390/ijms21031051 - 5 Feb 2020
Cited by 22 | Viewed by 4718
Abstract
The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially [...] Read more.
The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer considered a passive filler, bone marrow adipocytes have emerged as critical contributors to cancer progression. Released by adipocytes, adipokines are soluble factors with hormone-like functions and are currently believed to affect tumour development. Src-associated in mitosis of 68 kDa (Sam68), originally discovered as a protein physically associated with and phosphorylated by c-Src during mitosis, is now recognised as an important RNA-binding protein linked to tumour onset and progression of disease. Sam68 also regulates splicing events and recent evidence reports that dysregulation of these events is a key step in neoplastic transformation and tumour progression. The present review reports recent findings on adipokines and Sam68 and their role in breast cancer progression and metastasis. Full article
(This article belongs to the Special Issue Adiposity and Adipokines: Roles in the Local Spread of Cancer and the Metastasis Development)
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