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Okayama University Medical Research Updates (OU-MRU)Vol.95

October 11, 2021

Okayama University Medical Research Updates (OU-MRU) 2021.10 Vol.95
Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 11 October 2021
Okayama University research: Liquid biopsies: A new avenue for detecting cancer in the blood.

(Okayama, 7 October) In a study reported in the journal Cancers, researchers from Okayama University describe the use of MCT1, a molecule found in the blood, for the detection of synovial sarcoma.

Soft-tissue sarcoma is a cancer that originates in supportive tissues of the body such as muscles, cartilage, and fat. Methods for detecting and monitoring this rare form of cancer are relatively primitive and nonspecific. Now, a research team led by Assistant Professor FUJIWARA Tomohiro (M.D.) at Okayama University has discovered a molecule in the blood which can help predict the degree of synovial sarcoma.

The cells in our body release tiny sacs that contain biomolecules. The sacs, or extracellular vesicles (EVs), released from tumors contain substances specific to cancer cells. Now, EVs are secreted into the blood, making it easy to acquire them for diagnostic tests. To obtain more information about synovial sarcoma, the researchers first isolated and analyzed EVs secreted by various synovial sarcoma cells and circulating in patients with synovial sarcoma. One protein, monocarboxylate transporter 1 (MCT1), was found to be considerably higher in EVs from patients with synovial sarcoma compared to healthy individuals. What’s more, MCT1 was found attached to the outer membrane of these EVs, making is easy to track.

To better understand the diagnostic potential of MCT1 expressed on the EVs, mice were transplanted with synovial sarcoma cells and their blood was drawn after tumors started growing. MCT1 levels found in the blood closely correlated with tumor growth in these mice. Additionally, when the tumors were surgically removed from some of the mice, their MCT1 levels went down. These findings were then validated in humans, by assessing the blood from patients with synovial sarcoma before and after treatment.

Cancer patients are typically treated with chemotherapy (which shrinks the tumor) followed by resection of the tumor. When a cohort of such patients was studied, some patients with synovial sarcoma showed lower levels of MCT1 just after chemotherapy, but all showed reduced MCT1 levels after resection. When their tumors were closely analyzed, MCT1 was found located either on the surface of cells, or deep within the cells. However, patients with MCT1 found on the cell surface had the lowest chances of survival. MCT1 was helpful in distinguishing the tumor status of patients and predicting their response to treatment. Lastly, the team investigated the exact role of MCT1 in synovial sarcoma. When MCT1 was blocked in synovial sarcoma cells, the cells showed lower chances of survival, migration, and invasion of neighboring cells. It is thus likely that MCT1 directly contributes to the progression of synovial sarcoma.

“This work describes a new liquid biopsy technique to sensitively monitor synovial sarcoma using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in this tumor,” suggest the researchers. Given its role in accurately identifying the status of tumors and its contribution to the progression of tumors, MCT1 could be a promising target for development in the diagnosis and treatment of synovial sarcoma.

Background
Liquid biopsy:
Liquid biopsies are tests performed on blood, urine, or saliva that aid in the diagnosis of a disease. In the case of cancer, liquid biopsies are usually preferred as they eliminate the need to extract tumor tissues which often involves invasive procedures. These biopsies aid oncologists with early detection of disease, monitoring tumor growth and predicting a patient’s response to treatments. Thus, using liquid biopsy to track markers such as MCT1 can prove to be effective in the timely therapeutic intervention of patients with sarcoma.

Extracellular vesicles (EVs): EVs are tiny sacs released by cells into the surrounding medium. EVs contain proteins, fats, and other biomolecules and ferry them to neighboring and distant cells; this is typically how our cells communicate with each other. Since EVs must often traverse distances, they are found within tissues like blood and lymph that flow throughout the body. Tumor-borne EVs are a new target in cancer research as they are easy to capture and contain specific information about their parent cancer cells.

Reference
Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Shintaro Iwata, Tsukasa Yonemoto, Koji Ueda, Toshifumi Ozaki. Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. Cancers, 2021, 13(8), 1823.
DOI: 10.3390/cancers13081823.
https://www.mdpi.com/2072-6694/13/8/1823


Reference (Okayama Univ. e-Bulletin): Dr. FUJIWARA’s team
OU-MRU Vol.93:Repurposing cancer drugs: An innovative therapeutic strategy to fight bone cancer.

Correspondence to
Assistant Professor FUJIWARA Tomohiro, M.D.,Ph.D.
Department of Orthopaedic Surgery,
Graduate School of Medicine, Dentistry and Pharmaceutical Science,
Okayama University, 2-5-1 Shikata-cho, Kita-ku,
Okayama 700-8558, Japan
E-mail: tomomedvn(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

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The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75:More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76:The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77:Green leafy vegetables contain a compound which can fight cancer cells
Vol.78:Disrupting blood supply to tumors as a new strategy to treat oral cancer
Vol.79:Novel blood-based markers to detect Alzheimer’s disease
Vol.80:A novel 3D cell culture model sheds light on the mechanisms driving fibrosis in pancreatic cancer
Vol.81:Innovative method for determining carcinogenicity of chemicals using iPS cells
Vol.82:Making memories — the workings of a neuron revealed
Vol.83:Skipping a beat — a novel method to study heart attacks
Vol.84:Friend to Foe—When Harmless Bacteria Turn Toxic
Vol.85:Promising imaging method for the early detection of dental caries
Vol.86:Plates and belts — a toolkit to prevent accidental falls during invasive vascular proceduresa
Vol.87:Therapeutic potential of stem cells for treating neurodegenerative disease
Vol.88:Nanotechnology for making cancer drugs more accessible to the brain
Vol.89:Studying Parkinson’s disease with face-recognition software
Vol.90:High levels of television exposure affect visual acuity in children
Vol.91:Meeting high demand: Increasing the efficiency of antiviral drug production in bacteria
Vol.92:Numerical modelling to assist the development of a retinal prosthesis
Vol.93:Repurposing cancer drugs: An innovative therapeutic strategy to fight bone cancer
Vol.94:A berry vine found in Asia proves useful in combating lung cancer

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