Metabolic and Amino Acid Alterations of the Tumor Microenvironment

Abstract

: Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely alterations in metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of prostate cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from metabolism of other tissues. Findings from different tissues are therefore not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.

Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer

“…Moreover, the microbial glycolipid metabolism, amino acid metabolism, and oxidative stress of such perturbed lung microbial community were also enhanced. During inflammation and cancer, host immune cells or tumor cells need energy to support their physiological function, leading to increased anaerobic glycolysis and amino acid consumption (Fahrmann et al, 2020;Schiliro and Firestein, 2021;Stepka et al, 2021;Tome, 2021), which was consistent with our findings on the metabolic alteration of the lung microbiome. Thus, these changes may be associated with specific metabolic characteristics of COPD-related lung cancer.…”

Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

“…Hence, drugs with an acidic dissociation constant of 7.5-9.5 may show a significantly reduced rate of uptake, such as vincristine, mitoxantrone, doxorubicin, and vinblastine (Cowan and Tannock, 2001;Gerweck et al, 2006;Trédan et al, 2007;Zhou et al, 2019). Therefore, the cytotoxicity of these drugs is suppressed, resulting in a resistant phenotype (Raghunand et al, 2003;Trédan et al, 2007;Stepka et al, 2020). However, the concentration of some weakly acidic drugs including cyclophosphamide and chlorambucil may be increased in the neutral intracellular region (Gerweck et al, 2006;Trédan et al, 2007).…”

The Role of Intestinal Flora in Anti-Tumor Antibiotic Therapy

“…Numerous studies have explored the role of intestinal flora on tumor immune micro-environment and tumor treatment. Intestinal flora can also inhibit tumor proliferation, differentiation, and migration by producing metabolites, such as SCFAs, amino acids, indoles, and polyamines [43][44][45][46][47][48][49][50][51][52][53][54][55][56]. These metabolites participate in various signaling pathways that regulate immune function including antitumor immunity [43,[57][58][59].…”

“…The anti-tumor effects of intestinal microbiota metabolites have attracted much attention in recent years (Table 1, Ref. [28,[47][48][49][50][51]57,58,[67][68][69][70][71][72][73][74][75][76]). Protein metabolism occurs mainly in the intestine.…”