Just another obesity paradox in Hodgkin lymphoma?

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Just another obesity paradox in Hodgkin lymphoma?

Quarta, 02.11.2016

Authors and Affiliations:

Andreia Matos a, Joana Marinho-Dias b, Sofia Ramalheira c, Mário Mariz c, Maria J. Oliveira d, Manuel Bicho a, Ricardo Ribeiro a,b

a Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal;

b Molecular Oncology Group-CI, Portuguese Institute of Oncology, Edificio Laboratorios-Piso 4, Rua Dr António Bernardino Almeida, 4200-072 Porto, Portugal;

c Oncohematology Department, Portuguese Institute of Oncology Porto Centre, Rua Dr António Bernardino Almeida, 4200-072 Porto, Portugal;

d i3S-Instituto de Investigação e Inovação em Saúde/INEB-Institute of Biomedical Engineering, University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal;



Contemporary meta-analysis and prospective studies confirmed the positive association of body mass index with Hodgkin lymphoma (HL). Nevertheless, despite the continuously growing body of knowledge, the role of body adiposity in HL microenvironment remains unclear. We do know that excess adiposity influence tumor behavior through few mechanisms: 1) adipokines, 2) adipose-derived stem cell migration, 3) metabolism regulation, and by 4) modulating immunoinflammatory response 1. Moreover, the endocrine/paracrine interactions of soluble factors, both at its primary site and at preferential distant dissemination sites (e.g., bone marrow), cannot be negligible 1,2.

In our hypothesis-generating review, the biologically plausible links between excess adiposity and HL in light of recent basic and clinical data are explored, highlighting a molecular mechanistic model and, particularly, evidencing the potential role of adipocytes from the bone marrow in the metastatic niche 2.

Adding up to this review, recent, unpublished work from our lab has shown deregulated adipokine pathways and bone-derived factors in the bone marrow fluid from HL patients and controls. Notably, osteoprotegerin was altered in the bone marrow fluid from obese subjects, thereby influencing RANKL-mediated osteoclast recruitment and activation. Besides osteoprotegerin, also insulin growth factor-binding protein 3 was altered, suggesting a potential protective effect from adipokines at the bone-marrow microenvironment of HL patients, rendering obesity-HL association another paradoxical case of obesity protective influence in cancer, particularly advanced metastatic disease.

Knowledge of adipocyte biology in the context of malignancy is therefore crucial for understanding the pathophysiological basis of obesity associated with HL. The reprogrammed tumor-educated behavior of adipocytes likely provides a tumor-permissive metabolic, inflammatory, fibrotic, and angiogenic microenvironment that modulate HRS cell survival.


We acknowledge the support from a RayBiotech´s 2013 Innovative Research Grant.


1. Strong AL, Burow ME, Gimble JM, Bunnell BA, Concise review: The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells. Stem Cells 2015; 33 (2): 318-26.

2. Mareel M, Oliveira MJ, Madani I. Cancer invasion and metastasis: interacting ecosystems. Virchows Arch 2009; 454 (6): 599-622.

3. Matos A, Marinho-Dias J, Ramalheira S, Oliveira MJ, Bicho M, Ribeiro R. Mechanisms underlying the association between obesity and Hodgkin lymphoma. Tumour Biol 2016 (online first).


Journal: Tumor Biology


Link: http://link.springer.com/article/10.1007%2Fs13277-016-5198-4