Tumor macroenvironment and metabolism.
In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described.
Wael
W
Al-Zoughbi
Institute of Pathology, Medical University of Graz, Graz, Austria.
Wael
W
Al-Zhoughbi
Institute of Pathology, Medical University of Graz, Graz, Austria.
Jianfeng
J
Huang
Institute of Pathology, Medical University of Graz, Graz, Austria.
Ganapathy S
GS
Paramasivan
Department of Paediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria.
Holger
H
Till
Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Martin
M
Pichler
Institute of Pathology, Medical University of Graz, Graz, Austria.
Barbara
B
Guertl-Lackner
Institute of Pathology, Medical University of Graz, Graz, Austria. Electronic address: gerald.hoefler@medunigraz.at.
Gerald
G
Hoefler
D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000150:complications; D011506:Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D059016:Tumor Microenvironment
D000596:Amino Acids; D008055:Lipids; D011506:Proteins