Metabolic Interactions in the Tumor Microenvironment

Abstract

Tumors are dynamic pseudo-organs that contain numerous cell types interacting to create unique physiology. Within this network, the malignant cells encounter many challenges and rewire their metabolic properties accordingly. Such changes can be experienced and executed autonomously or through interaction with other cells in the tumor. The focus of this review is on the remodeling of the tumor microenvironment that leads to pathophysiologic interactions that are influenced and shaped by metabolism. They include symbiotic nutrient sharing, nutrient competition, and the role of metabolites as signaling molecules. Examples of such processes abound in normal organismal physiology, and such heterocelluar metabolic interactions are repurposed to support tumor metabolism and growth. The importance and ubiquity of these processes is just beginning to be realized, and insights into their role in tumor development and progression are being used to design new drug targets and cancer therapies.

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer

“…These findings will require further validation to establish the potential for biomarker use. An explanation for this observation could be that a metabolically active environment would better support a tumor and facilitate spread of cancer cells by either supplying them with healthy mitochondria or a nurturing environment …”

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

“…The extracellular lactate serves not only as a respiratory fuel for oxidative cells, but, together with the H + , contributes to an acidic tumor microenvironment and is meanwhile recognized as an important signaling molecule promoting migration, angiogenesis, and immunosuppression 27. The phenomenon of intratumoral lactate shuttling has been described for several solid tumors and is suggested to occur commonly across cancer types 28. Accordingly, aberrant expression of MCT1, MCT2, and/or MCT4 has been demonstrated e.g., in colon cancer, glioblastoma, breast cancer, prostate cancer, pancreatic cancer, or clear cell renal cell carcinoma 29, 30.…”

Hypoxia induced changes in miRNAs and their target mRNAs in extracellular vesicles of esophageal squamous cancer cells

“…at/cgi‐bin/RNAfold.cgi). The criteria for secondary structure prediction were: number of nucleotides in one bulge in stem (≤12) number of base pairs in the stem region of the predicted hairpin (≥16) cutoff of free energy (kCal/mol ≤−15) length of hairpin (top and bottom stems + terminal loop ≥50) length of hairpin loop (≤20) number of nucleotides in one bulge in mature region (≤8) number of biased errors in one bulge in mature region (≤4) number of biased bulges in mature region (≤2) number of errors in mature region (≤ 7) number of base pairs in the mature region of the predicted hairpin (≥ 12) percent of mature in stem (≥80).…”

“…This means that the radiation dose required to kill hypoxic cells is 2.5 to three times more than the dose required to kill aerobic cells . The tumor microenvironment (TME) is made up of different cell types, extracellular matrix, and numerous extracellular molecules . Accumulated evidence underscores the role of TME in promoting tumor formation and progression .…”