Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 17 March 2020
Okayama University research: Disrupting blood supply to tumors as a new strategy to treat oral cancer

(Okayama, 17 March) Researchers at Okayama University have recently published a study in Cells in which they reduced the size of oral cancer tumors by damaging the blood vessels surrounding the tumor cells.

Cancer cells have ingenious mechanisms of survival within the body. One strategy they adopt is developing a network of blood vessels around themselves as a source of blood supply. Scientists have long been investigating ways to prevent this blood flow to cancer cells. CXCR4 is a protein known to be closely involved with tumor growth. However, its exact role in tumor progression is unclear. A research team led by Assistant Professor KAWAI Hotaka and YOSHIDA Saori(graduate student, D.D.S.), Assistant Professor EGUCHI Takanori at Okayama University has now shown that CXCR4 is the main culprit maintaining the arrangement of tumor blood vessels.

Firstly they found, immunohistochemistry on human clinical specimens revealed that tumor vessels expressed CXCR4 in human oral cancer specimens. The next question to arise was whether the CXCR4-rich blood vessels were promoting tumor growth. In order to investigate this further, the oral cancer cells were transplanted into mice. Once the tumor growed in mice body, they were given AMD3100-a drug that antagonises CXCR4. When the tumors were subsequently observed under a microscope, several areas were found to necrotic. A characteristic pattern of necrosis was observed in which the tumor tissue that were at a distance away from the blood vessel was necrotic, leaving the tumor tissue close to the periphery of the blood vessel.. This randomized pattern of tumor cell death was termed ‘tumor angiogenic inhibition triggered necrosis’ (TAITN) by the researchers. The wide area of tumor tissue also showed a severe lack of oxygen which was accompanied by an impairment of angiogenesis. CXCR4 inhibition thus seemed to induce tumor necrosis by damaging the blood vessels and preventing the cells of a healthy oxygen supply.

This study is the first to show the role of CXCR4 in promoting tumor growth by supplying cancer cells with a healthy, organized network of blood vessels. Strategies that can disrupt this network can be explored further as anti-cancer therapies. “CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment”, concludes the team.


Background
CXCR4: CXCR4 is a protein vital in maintaining and growing the cells that produce blood within our body. In fetuses, CXCR4 is also responsible for the formation of certain blood vessels. Incidentally, CXCR4 is also present in various forms of cancers such as breast, liver, and oral cancer. Often, tumors which show the presence of CXCR4 tend to grow faster that those without. Given its link with blood vessels and cancer progression, the research team from Okayama University sought out to investigate whether CXCR4 directly promotes cancer growth by supplying tumors with blood.

Reference
Saori Yoshida, Hotaka Kawai*, Takanori Eguchi*, Shintaro Sukegawa, May Wathone Oo, Chang Anqi, Kiyofumi Takabatake, Keisuke Nakano, Kuniaki Okamoto, Hitoshi Nagatsuka. Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer. Cell, 2019, 8(7), 761.
DOI : 10.3390/cells8070761
Cells | Free Full-Text | Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) in Oral Cancer


Correspondence to
Assistant Professor KAWAI Hotaka, D.D.S.,Ph.D.
Department of Oral Pathology and Medicine,
Graduate School of Medicine, Dentistry and Pharmaceutical Science,
Okayama University, 2-5-1 Shikata-cho, Kita-ku,
Okayama 700-8558, Japan
E-mail:hotaka-k(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.


Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Public Relations Division
E-mail: www-adm(a)adm.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Website: //www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin: //www.okayama-u.ac.jp/user/kouhou/ebulletin/
We love OKAYAMA UNIVERSITY: https://www.youtube.com/watch?v=7cXlttQIk3E
Okayama University Image Movie（2018）
https://www.youtube.com/watch?v=WmyqOTuigBs


Okayama University Medical Research Updates （OU-MRU）
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