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Okayama University Medical Research Updates (OU-MRU) Vol.51

March 19, 2018

Source: Okayama University (JAPAN), Public Relations and Information Strategy
For immediate release: 16 March 2018
Okayama University research: Potential of 3D nanoenvironments for experimental cancer

(Okayama, 16 March) Researchers at Okayama University employed a 3D nano-matrix to gain insights into how different cells types mimic the properties of cancer stem cells in this environment. Their results published in the journal PLOS One shows that a nano-environment promotes distinct patterns of cell aggregation and biological properties that are reminiscent of tumors.

In biological experiments cells are usually grown on a two-dimensional matrices. Although cells stick well to such surfaces, this process of adhesion can sometimes mask the natural biological properties of cells. So there is demand for alternatives to 2D matrix environments to cultivate and study cancer cells. NanoCulture Plates (NCP) are specialized nano-scale matrices, resembling the scaffolding on a building. NCPs give cells space to migrate freely without adhering to the bottom and aggregation with each other; all of these properties are essential for tumors.

Dr. Takanori Eguchi and colleagues at Okayama University adopted these favorable properties of NCPs to study the properties of 67 biological cell lines, focusing on the range of cells that could successfully transform into cancerous cells. A remarkable feature of cancer cells is their ability to grow in the body even under conditions of low oxygen. Under these conditions, cancer cells tend to start showing properties of stem cells, thus forming ‘cancer stem cells’ (CSC). The milieu inside cell aggregates can also result in oxygen deprivation. The authors were thus also interested in seeing if CSCs could be induced in NCPs. To sustain the induction of ‘stemness’, a growth medium containing enhanced nutrients was used, termed a stem cell inducing medium.

The researchers observed that while most of the cell lines formed ‘spheroids’ characteristic of tumor cells, a novel pattern of ‘grape-like aggregation (GLA)’ was also prominent in some cases. To characterize GLA forming cells further, cells known as PC-3 cells were grown on NCPs and then injected into mice. Not only did PC-3 GLAs enlarge into tumors, but they also rapidly migrated to other organs just like cancer cells, while the spheroids did not show such behavior. The presence of the stem cell inducing medium in NCPs further favored the formation of larger aggregates of PC-3 cells, with very strong intercellular adhesion forces, reminiscent of CSCs.

CSCs have an unusual genetic profile, comprising stem cell genes and cancer cell genes. Incubation of PC-3 cells in NCPs resulted in induction of a high number of pluripotency or ‘stemness’ inducing genes, along with some tumor inducing genes. CSCs also secret intracellular sacs called exosomes, which contain EpCAM- one of CSC proteins. By studying the extracellular fluid, the researchers found that exosome-free HSP90α was also abundantly released under these conditions.

In this study, NCPs were seen to be an excellent mactices for replicating in-vitro tumor synthesis. The authors anticipate that, “These features of NCPs may be useful for advanced tumor and stem cell biology and preclinical testing of novel therapeutics.”

Background
Cancer stem cells: Stem cells are cells with the enhanced ability to evolve into any cell type. Cancer stem cells are thus cells found within tumors, with this ability. These cells are highly lethal because owing to their enhanced potential, they can lead to relapse of tumors.

Pluripotency: Ability of certain cells to change into any other cell type in the body, with distinct properties and functions. Stem cells are thus an example of cells having pluripotency.

Reference
Takanori Eguchi, Chiharu Sogawa, Yuka Okusha, Kenta Uchibe, Ryosuke Iinuma, Kisho Ono, Keisuke Nakano, Jun Murakami, Manabu Itoh, Kazuya Arai, Toshifumi Fujiwara, Yuri Namba, Yoshiki Murata, Kazumi Ohyama, Manami Shimomura, Hirohiko Okamura, Masaharu Takigawa, Tetsuya Nakatsura, Kenichi Kozaki, Kuniaki Okamoto, Stuart K. Calderwood. Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment. PLOS One, 2018 Feb 7;13(2):e0191109.
DOI: 10.1371/journal.pone.0191109. eCollection 2018.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191109


Correspondence to
Assistant Professor Takanori Eguchi, D.D.S., Ph.D.
Department of Dental Pharmacology,
Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, Shikata-cho 2-5-1, Okayama
city, Okayama 700-8558, Japan
E-mail: eguchi(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
https://scholar.google.com/citations?hl=en&user=d37h9nQAAAAJ&view_op=list_works&sortby=pubdate

Further information
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Okayama University Medical Research Updates (OU-MRU)Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testingVol.2:Ensuring a cool recovery from cardiac arrestVol.3:Organ regeneration research leaps forwardVol.4:Cardiac mechanosensitive integratorVol.5:Cell injections get to the heart of congenital defectsVol.6:Fourth key molecule identified in bone developmentVol.7:Anticancer virus solution provides an alternative to surgeryVol.8:Light-responsive dye stimulates sight in genetically blind patientsVol.9:Diabetes drug helps towards immunity against cancerVol.10:Enzyme-inhibitors treat drug-resistant epilepsyVol.11:Compound-protein combination shows promise for arthritis treatmentVol.12:Molecular features of the circadian clock system in fruit fliesVol.13:Peptide directs artificial tissue growthVol.14:Simplified boron compound may treat brain tumoursVol.15:Metamaterial absorbers for infrared inspection technologiesVol.16:Epigenetics research traces how crickets restore lost limbsVol.17:Cell research shows pathway for suppressing hepatitis B virusVol.18:Therapeutic protein targets liver diseaseVol.19:Study links signalling protein to osteoarthritisVol.20:Lack of enzyme promotes fatty liver disease in thin patientsVol.21:Combined gene transduction and light therapy targets gastric cancerVol.22:Medical supportive device for hemodialysis catheter punctureVol.23:Development of low cost oral inactivated vaccines for dysenteryVol.24:Sticky molecules to tackle obesity and diabetesVol.25:Self-administered aroma foot massage may reduce symptoms of anxietyVol.26:Protein for preventing heart failureVol.27:Keeping cells in shape to fight sepsisVol.28:Viral-based therapy for bone cancerVol.29:Photoreactive compound allows protein synthesis control with lightVol.30:Cancer stem cells’ role in tumor growth revealedVol.31:Prevention of RNA virus replicationVol.32:Enzyme target for slowing bladder cancer invasionVol.33:Attacking tumors from the insideVol.34:Novel mouse model for studying pancreatic cancerVol.35:Potential cause of Lafora disease revealedVol.36:Overloading of protein localization triggers cellular defectsVol.37:Protein dosage compensation mechanism unravelledVol.38:Bioengineered tooth restoration in a large mammalVol.39:Successful test of retinal prosthesis implanted in ratsVol.40:Antibodies prolong seizure latency in epileptic miceVol.41:Inorganic biomaterials for soft-tissue adhesionVol.42:Potential drug for treating chronic pain with few side effectsVol.43:Potential origin of cancer-associated cells revealedVol.44:Protection from plant extractsVol.45:Link between biological-clock disturbance and brain dysfunction uncoveredVol.46:New method for suppressing lung cancer oncogeneVol.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

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