Anti ‐tumor effects of an antagonistic mAb against the ASCT2 amino acid transporter on KRAS‐mutated human colorectal cancer cells

This study strongly suggests that ASCT2 is an excellent target molecule for the treatment of malignancies, especiallyKRAS‐mutated cancers. AbstractKRAS mutations are detected in numerous human cancers, but there are few effective drugs forKRAS‐mutated cancers. Transporters for amino acids and glucose are highly expressed on cancer cells, possibly to maintain rapid cell growth and metabolism. Alanine‐serine‐cysteine transporter 2 (ASCT2) is a primary transporter for glutamine in cancer cells. In this study, we developed a novel mono clonal antibody (mAb) recognizing the extracellular domain of human ASCT2, and investigated whether ASCT2 can be a therapeutic target forKRAS‐mutated cancers. Rats were immunized with RH7777 rat hepatoma cells expressing human ASCT2 fused to green fluorescent protein (GFP). Splenocytes from the immunized rats were fused with P3X63Ag8.653 mouse myeloma cells, and selected and cloned hybridoma cells secreting Ab3‐8 mAb were established . This mAb reacted with RH7777 transfectants expressing ASCT2‐GFP proteins in a GFP intensity‐dependent manner. Ab3‐8 reacted with various human cancer cells, but not with non‐cancer breast epithelial cells orASCT2‐knocked out HEK293 and SW1116 cells. In SW1116 and HCT116 human colon cancer cells withKRAS mutations, treatment with Ab3 ‐8 reduced intracellular glutamine transport, phosphorylation of AKT and ERK, and inhibited in vivo tumor growth of these cells in athymic mice. Inhibition of in v...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research

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This study investigated the protein expression profile of STC1 in PCa and benign prostatic hyperplasia (BPH) samples and STC1 signalling during cell proliferation and cell death in vitro using cell lines. We found higher levels of STC1 in PCa when compared to BPH tissue and that STC1 inhibited forskolin stimulation of cAMP in PC-3 cells. A monoclonal antibody against STC1 was effective in reducing cell proliferation, in promoting cell cycle arrest, and in increasing apoptosis in the same cells. Since STC1 acts as a regulator of prostatic tissue signalling, we suggest that this protein is a novel candidate biomarker for p...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
Publication date: Available online 6 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Lorenzo GalluzziAlthough somatic KRAS mutations are common in human tumors, no inhibitor of mutant KRAS was clinically available until recently. Canon and colleagues describe the ability of a clinically available KRASG12C inhibitor to drive immunogenic cancer cell death, thus constituting a promising combinatorial partner for immune checkpoint blockers.
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
ConclusionABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women.
Source: Saudi Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
ConclusionThe findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP.
Source: Saudi Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
ConclusionResults of this study demonstrated the potential of MWL oil in the development of natural anticancer therapeutic agents.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 6 December 2019Source: International Journal of PharmaceuticsAuthor(s): Iftikhar Khan, Maria Apostolou, Ruba Bnyan, Chahinez Houacine, Abdelbary Elhissi, Sakib S YousafAbstractA simplistic approach was conducted to manufacture novel paclitaxel (PTX) loaded protransfersome tablet formulations for pulmonary drug delivery. Large surface area presented by pulmonary system offer better target using anti-cancer drug deposition for localized effect in the lungs. Protransfersomes are dry powder formulations, whereas transfersomes are liquid dispersions containing vesicles generated from protransf...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Conclusion: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.Graphical abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 22 October 2019Source: Seminars in Cancer BiologyAuthor(s): Tamara T. Lah, Metka Novak, Barbara BreznikAbstractBrain, the major organ of the central nervous system controls and processes most of body activities. Therefore, the most aggressive brain tumor – glioblastoma and metastases from other organs to the brain are lethal leaving the patients with very short time of survival. The brain tissue landscape is very different from any other tissues and the specific microenvironment, comprising stem cells niches and blood-brain barrier, significantly influences the low rate of glioblast...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: March 2020Source: Journal of Cancer Policy, Volume 23Author(s): Brandon Maser, Lisa M. Force, Paola Friedrich, Federico Antillon, Ramandeep S. Arora, Cristian A. Herrera, Carlos Rodriguez-Galindo, Rifat Atun, Avram DenburgAbstractTo help understand how health systems and sociopolitical contexts intersect with and impact the performance of childhood cancer care in low- and middle-income countries (LMICs), we have developed a systems-level framework for analyzing the performance of LMIC childhood cancer programs within their health system contexts: The Paediatric Oncology System Integration Tool (POSIT). PO...
Source: Journal of Cancer Policy - Category: Cancer & Oncology Source Type: research
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Prashant Trikha, Dean A. LeeAbstractThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor (TF) that is a member of the Per-Arnt-Sim family of proteins. AhR regulates diverse processes, including malignant transformation, hematopoietic cell development, and fate determination of immune cell lineages. Moreover, AhR forms a crucial link between innate and adaptive arms of the immune system. Malignant cells frequently evolve multiple mechanisms for suppressing tumor-specific res...
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research
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