sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&amp;9 axis

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

Background

About 90% of cancer-related deaths are due to metastasis of cancer cells, and angiogenesis is a critical step in this process. sFLT01 is a novel fusion protein and a dual-targeting agent that neutralizes both VEGF and PlGF proangiogenic activities. GRP78 dual effect in tumor growth and angiogenesis could be activated under VEGF stimulation. The current study was designed to investigate the inhibitory impact of sFLT01 protein on VEGF/GRP78 axis. To this point, sFLT01 construct was synthesized, recombinant plasmid was expressed in eukaryotic host cells, sFLT01-HisTag protein was extracted and analyzed. The functional activity of sFLT01 on VEGF-enhanced tube formation and angiogenesis of HUVEC cells were examined. Eventually, the inhibitory impact of sFLT01 on growth, invasiveness, and migration of human prostate cancer cell line, DU145, was assessed. Real-time PCR evaluated the level of GRP78 and its effect on the downstream factors; matrix metallopeptidase proteins 2&9 (MMP2&9) along with tissue inhibitor of metalloproteinase proteins1&2 (TIMP1&2) under sFLT01 stimulation.

Results

According to the data, sFLT01 protein showed modulatory impact on proliferation, invasion, and migration of DU145 cells along with the potential of HUVECs angiogenesis. Real-Time PCR analysis depicted a significant downregulation in GRP78, MMP2 and MMP9 transcripts’ levels, and a subsequent elevation of TIMP1 and TIMP2 expression under sFLT01 stimulation was detected.

Conclusion

Overall, these data indicated that the inhibitory impact of sFLT01 on cancer cells growth and invasiveness could be mediated through the modulation of VEGF/GRP78/MMP2&9 axis and activation of TIMPs.

Related collections

Most cited references 47

Record: found
Abstract: found
Article: not found

Cancer statistics, 2019

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.

0 comments Cited 6483 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Tumor angiogenesis: causes, consequences, challenges and opportunities

Roberta Lugano, Mohanraj Ramachandran, Anna Dimberg (2019)

Tumor vascularization occurs through several distinct biological processes, which not only vary between tumor type and anatomic location, but also occur simultaneously within the same cancer tissue. These processes are orchestrated by a range of secreted factors and signaling pathways and can involve participation of non-endothelial cells, such as progenitors or cancer stem cells. Anti-angiogenic therapies using either antibodies or tyrosine kinase inhibitors have been approved to treat several types of cancer. However, the benefit of treatment has so far been modest, some patients not responding at all and others acquiring resistance. It is becoming increasingly clear that blocking tumors from accessing the circulation is not an easy task to accomplish. Tumor vessel functionality and gene expression often differ vastly when comparing different cancer subtypes, and vessel phenotype can be markedly heterogeneous within a single tumor. Here, we summarize the current understanding of cellular and molecular mechanisms involved in tumor angiogenesis and discuss challenges and opportunities associated with vascular targeting.

0 comments Cited 441 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Endothelial cell migration during angiogenesis.

Laurent Lamalice, Fabrice Le Boeuf, Jacques Huot (2007)

Endothelial cell migration is essential to angiogenesis. This motile process is directionally regulated by chemotactic, haptotactic, and mechanotactic stimuli and further involves degradation of the extracellular matrix to enable progression of the migrating cells. It requires the activation of several signaling pathways that converge on cytoskeletal remodeling. Then, it follows a series of events in which the endothelial cells extend, contract, and throw their rear toward the front and progress forward. The aim of this review is to give an integrative view of the signaling mechanisms that govern endothelial cell migration in the context of angiogenesis.

0 comments Cited 415 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Zahra-Soheila Soheili: soheili@nigeb.ac.ir

Journal

Journal ID (nlm-ta): BMC Mol Cell Biol

Journal ID (iso-abbrev): BMC Mol Cell Biol

Title: BMC Molecular and Cell Biology

Publisher: BioMed Central (London )

ISSN (Electronic): 2661-8850

Publication date (Electronic): 19 May 2021

Publication date PMC-release: 19 May 2021

Publication date Collection: 2021

Volume: 22

Electronic Location Identifier: 30

Affiliations

[1 ]GRID grid.419420.a, ISNI 0000 0000 8676 7464, Department of Molecular Medicine, , National Institute of Genetic Engineering and Biotechnology, ; 14965/161, Tehran, Iran

[2 ]GRID grid.418552.f, Blood Transfusion Research Center, , High Institute for Research and Education in Transfusion Medicine, ; Tehran, Iran

[3 ]GRID grid.38142.3c, ISNI 000000041936754X, Molecular Biomarkers Nano-Imaging Laboratory, , Brigham and Women’s Hospital, Department of Radiology Harvard Medical School, ; Boston, MA USA

Article

Publisher ID: 367

DOI: 10.1186/s12860-021-00367-5

PMC ID: 8135984

PubMed ID: 34011277

SO-VID: 4715d225-2044-4394-acc2-6de9e2c946a1

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 30 January 2021

Date accepted : 20 April 2021

Custom metadata

Keywords: prostate cancer,angiogenesis,sflt01,vegf,grp78

Data availability:

Keywords: prostate cancer, angiogenesis, sflt01, vegf, grp78

Comments

Comment on this article

scite_

Cited by 3

See all cited by

Most referenced authors 725

See all reference authors

- Version 1

sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis

Read this article at

Abstract

Background

Results

Conclusion

Related collections

Gamma Delta T cells

Most cited references 47

Cancer statistics, 2019

Tumor angiogenesis: causes, consequences, challenges and opportunities

Endothelial cell migration during angiogenesis.

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 348

Cited by 3

Most referenced authors 725