Journal article
Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44
PloS one, Vol.12(3), pp.e0173400-e0173400
2017
DOI: 10.1371/journal.pone.0173400
PMCID: PMC5338862
PMID: 28264026
Abstract
Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model. Melanoma cells exiting fragments of three independent melanomas or from secondary cultures derived from them, and cells from the melanoma line HTB-66, all underwent coalescence mediated by specialized cells in the 3D model. Normal melanocytes did not. However, coalescence of melanoma cells differed from that of breast-derived tumorigenic cell lines in that they 1) coalesced immediately, 2) underwent coalescence as individual cells as well as aggregates, 3) underwent coalescence far faster and 4) ultimately formed long, flat, fenestrated aggregates that were extremely dynamic. A screen of 51 purified monoclonal antibodies (mAbs) targeting cell surface-associated molecules revealed that two mAbs, anti-beta 1 integrin/(CD29) and anti-CD44, blocked melanoma cell coalescence. They also blocked coalescence of tumorigenic cells derived from a breast tumor. These results add weight to the commonality of coalescence as a characteristic of tumorigenic cells, as well as the usefulness of the 3D Matrigel model and software for both investigating the mechanisms regulating tumorigenesis and screening for potential anti-tumorigenesis mAbs.
Details
- Title: Subtitle
- Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44
- Creators
- Deborah Wessels - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaDaniel F Lusche - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaEdward Voss - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaSpencer Kuhl - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaEmma C Buchele - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaMichael R Klemme - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaKanoe B Russell - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaJoseph Ambrose - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaBenjamin A Soll - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of AmericaAaron Bossler - Department of Molecular Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA United States of AmericaMohammed Milhem - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA United States of AmericaCharles Goldman - Mercy Hospital System of Des Moines, Des Moines, IA United States of AmericaDavid R Soll - Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.12(3), pp.e0173400-e0173400
- DOI
- 10.1371/journal.pone.0173400
- PMID
- 28264026
- PMCID
- PMC5338862
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Biology; Internal Medicine
- Record Identifier
- 9984047653302771
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