Mechanism of determining the invasive pattern of SCC

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21262
• Project/Area Number (Other): 18H06148 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kitasato University
• Principal Investigator: Kato Takuya 北里大学, 医学部, 助教 (00551970)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 癌細胞浸潤

Outline of Final Research Achievements

Cancers frequently invade as collective units. However, these invading units can be organized in a variety of ways, ranging from thin discontinuous strands to thick collectives. We employed 3D invasion assays to identify the factors that determine the mode of collective cancer cell invasion. We found that both matrix proteolysis and cell-cell junctions are required for the formation of wide strands, but only cell-cell junction has large effect on the maximum extent of invasion in certain contexts. Unexpectedly, the ability to generate wide invasive strands is coupled to the ability to grow effectively when surrounded by ECM in 3D assays. Cell-cell junction dependent strand widening requires localization of Actomyosin contractility to outer rim of the cell groups. In vivo, combinatorial perturbation of both matrix proteolysis and cell-cell adhesion demonstrated that the most aggressive cancer behavior is achieved at high levels of cell-cell adhesion and high levels of proteolysis.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では癌組織で見られる様々な形態がどのように形成されるのかを追求した。癌組織の形態は病理診断を下す際に重要な情報となるものであるが、それらの形態が実際にどのような癌細胞の性質に繋がるのかは明らかではなかった。今回の研究成果から、隣接組織に浸潤した癌細胞が浸潤した先で効率よく増殖する（≒浸潤部位の形態を肥厚化させる）ためには細胞外基質の分解能と細胞間の接着が重要であることが明らかになり、さらにその性質が転移にも影響することが分かった。具体的なメカニズムとして細胞集団内におけるアクトミオシン活性の偏在が重要であることが判明したため、今後はこの機構を標的とした治療法の開発につながると期待できる。