Targeting CD36 as Biomarker for Metastasis Prognostic: How Far from Translation into Clinical Practice?

Abstract

Metastasis requires cellular changes related to cell-to-cell and cell-to-matrix adhesion, immune surveillance, activation of growth and survival signalling pathways, and epigenetic modifications. In addition to tumour cells, tumour stroma is also modified in relationship to the primary tumour as well as to distant metastatic sites (forming a metastatic niche). A common denominator of most stromal partners in tumour progression is CD36, a scavenger receptor for fatty acid uptake that modulates cell-to-extracellular matrix attachment, stromal cell fate (for adipocytes, endothelial cells), TGFβ activation, and immune signalling. CD36 has been repeatedly proposed as a prognostic marker in various cancers, mostly of epithelial origin (breast, prostate, ovary, and colon) and also for hepatic carcinoma and gliomas. Data gathered in preclinical models of various cancers have shown that blocking CD36 might prove beneficial in stopping metastasis spread. However, targeting the receptor in clinical trials with thrombospondin mimetic peptides has proven ineffective, and monoclonal antibodies are not yet available for patient use. This review presents data to support CD36 as a potential prognostic biomarker in cancer, its current stage towards achieving bona fide biomarker status, and knowledge gaps that must be filled before further advancement towards clinical practice.

Evaluation of immune‑biomarker expression in high‑grade soft‑tissue sarcoma: HLA‑DQA1 expression as a prognostic marker

“…CD36 has a role in immune signaling and is also a scavenger receptor for fatty acid uptake that modulates cell-to-extracellular matrix attachment and TGF-β activation. CD36 has increasingly emerged as a prognostic marker associated with the metastatic process ( 22 ). Complement C3 is useful in the development of novel strategies to improve the effectiveness of cancer immunotherapy ( 23 ).…”

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate

“…CD36 signaling can lead to programmed cell death in other cell types, as showed by Rusiñol et al, [19] with hamster ovarian cells transfected with CD36. It has been proposed that fatty acid and cholesterol uptake may play a key role in proliferation and cell survive, and their oxidation during exercise may change the prostate epithelium [20,21]. Surprisingly, little attention has been paid to the role of physical exercise as a potential regulator of fatty acid oxidation and metabolism in prostate.…”

Psi promotesDrosophilawing growth through transcriptional repression of key developmental networks

“…emp possesses homology with mammalian CD36, a glycoprotein that responds to lipids, glycoproteins and lipoproteins to regulate angiogenesis and fatty acid uptake. CD36-null mice display elevated CD36 may have potential as a prognostic marker for metastatic cancer of epithelial origin (Enciu, Radu, Popescu, Hinescu, & Ceafalan, 2018;Ladanyi et al, 2018;Nath, Li, Roberts, & Chan, 2015). Here we demonstrate emp loss-of-function suppresses the Psi phenotype, which suggests direct repression of emp transcription by Psi is normally required to constrain wing growth.…”