Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Vasculogenic mimicry ( VM) formation by cancer cells is known to play a crucial role in tumor progression, but its detailed mechanism is unclear. In the present study, we focused on integrin β1 ( ITGB1) and assessed the role of ITGB1 in VM formation. We used in vitro methods to seed cancer cells on Matrigel to evaluate the capability of VM formation. We carried out ITGB1 gene deletion using the CRISPR/Cas9 system, and these ITGB1‐knockout cells did not show a VM‐like network formation. Further, reintroduction of ITGB1 rescued VM‐like network formation in ITGB1‐knockout cells. In conclusion, ITGB1 is a critical factor in VM of human cancer cells, and inhibition of ITGB1 may be a novel therapeutic approach for malignant cancer.

Related collections

Most cited references 29

Record: found
Abstract: found
Article: not found

Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry.

A. Maniotis, R Folberg, A. Hess … (1999)

Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.

0 comments Cited 558 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions.

Michael D. Schaller (2010)

Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are related tyrosine kinases that have important cellular functions, primarily through regulation of the cytoskeleton. Recent studies have identified multiple molecular mechanisms that regulate cytoskeletal responses, and have provided important and exciting insights into how FAK and Pyk2 control cellular processes such as cell migration. Equally exciting are reports of novel and originally unanticipated functions of these kinases, providing the groundwork for future avenues of investigation. This Commentary summarizes some of these recent discoveries that are relevant to the control of biological responses of the cell.

0 comments Cited 193 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The FERM domain: organizing the structure and function of FAK.

Margaret Frame, Hitesh Patel, Bryan Serrels … (2010)

Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain. Recent structural work reveals that regulatory protein partners convert auto-inhibited FAK into its active state by binding to its FERM domain. Further, the identity of FAK FERM domain-interacting proteins yields clues as to how FAK coordinates diverse cellular responses, including cell adhesion, polarization, migration, survival and death, and suggests that FERM domains might mediate information transfer between the cell cortex and nucleus. Importantly, the FAK FERM domain might act as a paradigm for the actions of other FERM domain-containing proteins.

0 comments Cited 110 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Siro Simizu: simizu@applc.keio.ac.jp

Journal

Journal ID (nlm-ta): Cancer Sci

Journal ID (iso-abbrev): Cancer Sci

Journal ID (doi): 10.1111/(ISSN)1349-7006

Journal ID (publisher-id): CAS

Title: Cancer Science

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1347-9032

ISSN (Electronic): 1349-7006

Publication date (Electronic): 09 July 2018

Publication date (Print): August 2018

Volume: 109

Issue: 8 ( doiID: 10.1111/cas.2018.109.issue-8 )

Pages: 2490-2496

Affiliations

[ ¹ ] Department of Applied Chemistry Faculty of Science and Technology Keio University Yokohama Japan

Author notes

[*] [* ] Correspondence: Siro Simizu, Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Kohoku‐ku, Yokohama, Japan ( simizu@ 123456applc.keio.ac.jp ).

Author information

Yuki Niwa http://orcid.org/0000-0001-8991-0155

Article

Publisher ID: CAS13693

DOI: 10.1111/cas.13693

PMC ID: 6113431

PubMed ID: 29900640

SO-VID: 9162bbc7-ef6d-449f-bec6-639c33023703

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 19 March 2018

Date revision received : 01 June 2018

Date accepted : 08 June 2018

Page count

Figures: 5, Tables: 0, Pages: 7, Words: 4566

Funding

Funded by: Japan Society for the Promotion of Science

Funded by: Grant‐in‐Aid for Young Scientists (B)

Award ID: JP17K15094

Custom metadata

source-schema-version-number 2.0

component-id cas13693

cover-date August 2018

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.4 mode:remove_FC converted:29.08.2018

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: crispr/cas9,focal adhesion kinase,integrin β1,metastasis,vasculogenic mimicry

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: crispr/cas9, focal adhesion kinase, integrin β1, metastasis, vasculogenic mimicry

Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells

Read this article at

Abstract

Related collections

Karger: Oncology

Most cited references 29

Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry.

Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions.

The FERM domain: organizing the structure and function of FAK.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 764

Cited by 25

Most referenced authors 920