Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.101

March 25, 2022

Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 25 March 2022
Okayama University research: Oral tumor progression mechanism identified

(Okayama, 25 March) Researchers at Okayama University report in JCI Insight the biomolecular mechanism underlying the progression of oral squamous cell carcinoma, a common tumor of the head and neck. The finding is likely to be relevant for developing oral cancer treatment strategies.

Oral squamous cell carcinoma (OSCC), a common type of tumor in the head and the neck, consists of, among other components, stroma — a heterogeneous group of cells that provides structure to a tissue. Recent research has revealed that OSCC patients with a high proportion of stroma in the tumor have a worse prognosis. Intending to develop potential treatment, understanding the role of stroma in driving OSCC progression is crucial. Now, Assistant Professor KAWAI Hotaka (D.D.S., Ph.D.) and May Wathone Oo (graduate student) at Okayama University has identified the mechanism responsible for OSCC growth: the tumor ‘recruits’ a particular kind of bone marrow-derived cells, a process facilitated by the presence of a specific compound expressed in cancer stroma.

First, the researchers isolated patient-derived cancer stroma cells for in vitro investigations. Assistant Professor KAWAI and colleagues then transplanted a tumor/stroma complex into green fluorescent protein-positive bone marrow cells transplanted mouse. The fluorescent protein is relatively easy to localize with imaging methods. So the migration of the bone-marrow cells could be followed over several weeks, during which the tumor evolved. These in vivo experiments confirmed that bone marrow-derived cells were recruited into the tumor microenvironment.

The scientists then checked which particular kinds of bone marrow-derived cells are recruited into the tumor. By marking the various candidate types by different marker molecules, they found that a type known as myeloid-derived suppressor cells (MDSCs) are recruited; these are cells that have immunosuppressive functions.

In a last set of experiments, Assistant Professor KAWAI and colleagues were able to identify the main factor in the recruitment mechanism of MDSCs into the tumor microenvironment. They established that patient-derived stroma produces high amounts of a protein called CCL2. Then, when artificially inhibiting the synthesis of CCL2, it was seen that the number of MDSCs decreased — an indication that CCL2 is indeed an enabler for MDSC recruitment.

Myeloid-derived suppressor cells (MDSCs) are a group of immune cells originating from bone marrow stem cells. MDSCs are implicated in pathological situations, including chronic infections and cancer. They have strong immunosuppressive activities (as opposed to immunostimulatory properties associated with other myeloid cell types) that play a role in regulating the functions of other immune cells.

The action mechanisms of MDSCs are not completely clear, but it has been established from clinical evidence that cancer tissues with a high content of MDSCs are linked with poor patient prognosis and resistance to therapies.

Assistant Professor KAWAI Hotaka and May Wathone Oo at Okayama University have now studied the link between MDSCs and oral squamous cell carcinoma progression and identified the critical resident stromal factor for the recruitment of MDSCs in OSCC.

May Wathone Oo, Hotaka Kawai, Kiyofumi Takabatake, Shuta Tomida, Takanori Eguchi, Kisho Ono, Qiusheng Shan, Toshiaki Ohara, Saori Yoshida, Haruka Omori, Shintaro Sukegawa, Keisuke Nakano, Kuniaki Okamoto, Akira Sasaki, and Hitoshi Nagatsuka. Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment. JCI insight. 2022;7(1):e148960.

Reference (Okayama University e-Bulletin & OU-MRU) : Assistant Professor KAWAI’s team
OU-MRU Vol.78:Disrupting blood supply to tumors as a new strategy to treat 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.

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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
Vol.95:A new avenue for detecting cancer in the blood
Vol.96:Automated cell image analysis
Vol.97:Artificial intelligence helps to determine cancer invasion
Vol.98:Okayama University launches clinical trials of a jawbone regeneration therapy using human BMP-2 transgenic protein derived from Escherichia coli.
Vol.99:A rapid flow process that can convert droplets into multilayer polymeric microcapsules
Vol.100:Understanding insect leg regeneration