Page 8 - Read Online

J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 3 of 27

organ regulating metabolic/immune processes with a central role in obesity-associated morbidities. AT is
composed of different cell types, i.e., adipocytes and almost a full spectrum of immune cells whose function
is changed in obesity. The AT inflammatory process affects adipocyte metabolism and secretory profile and
promotes activation of AT resident immune cells. The obesity-associated changes of this tissue are consistent
with an emerging concept that immune and metabolic systems are interconnected. Notably, dietary patterns
have been associated with increased/decreased CRC risk highlighting the importance of nutrients in cancer
prevention.

Experimental model: Visceral AT samples collected from lean and obese subjects affected or not by CRC
were assessed for immune cell, inflammatory and fatty acid (FA) profile as well as secretory function.

Results: Alterations of AT microenvironment including FA profile, inflammatory status, immune cell and
secretory pattern are found in obesity and CRC. Dietary polyunsaturated FA endowed with anti- or pro-
inflammatory properties are able to attenuate or exacerbate, respectively, AT inflammation.

Conclusion: AT inflammation has a key role in carcinogenesis and hyper-activated inflammatory pathways
in adipocytes can subvert immune surveillance. Dissecting the complexity of events associated with and/
or driving cancer development in obesity will open new avenues for lifestyle-targeted CRC prevention
strategies.

3. Monocarboxylate Transporters as targets for cancer therapy

Fátima Baltazar 1,2

1 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de
Gualtar, Braga 4710-057, Portugal.
2 ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães 4806-909, Portugal.

Preference for glucose metabolism is a common feature of cancer cells. They rely mainly on glycolysis
for adenoside triphosphate (ATP) production, with increased glucose uptake and lactic acid production,
leading to acidification of the microenvironment. This metabolic phenotype is associated with features
of cancer aggressiveness, including invasion, metastasis, evasion from the immune system, angiogenesis
and resistance to therapy. To cope with the high production of acids, cancer cells depend on the activity
of proton exchangers and transporters, which export protons to the microenvironment. Among these, are
monocarboxylate transporters (MCTs), which play a dual role in tumours, by removing lactate from the
cancer cells and also helping in the regulation of intracellular pH. Thus, considering their role in cancer,
MCTs represent attractive targets in cancer therapy.

We have studied the expression of MCTs in a variety of human cancer tissues including glioblastoma (GBM)
by immunohistochemistry and also blocked MCT activity in different in vitro and in vivo models. MCT1
and MCT4 were found to be overexpressed in human GBM samples compared with diffuse astrocytomas
and non-neoplastic samples. MCT1 targeting decreased cell glycolytic metabolism, migration, and invasion,
induced cell death and sensitized GBM cells to temozolomide in vitro, and reduced tumour size and
angiogenesis in vivo. Additionally, MCT1 is involved in the crosstalk between glioma cells and endothelial
cells, and MCT1 targeting either in the tumour cells or endothelial cells decreased endothelial cell
proliferation, migration and vessel assembly.

MCT1 is overexpressed in human gliomas and its inhibition decreased cancer cell aggressiveness
and sensitized cancer cells to chemotherapy. Additionally, MCT1 mediates endothelial cell metabolic