title: Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44.
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.
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Wessels
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Lusche
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Voss
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Spencer
authors.initials: S
authors.lastname: Kuhl
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Buchele
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Klemme
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Kanoe B
authors.initials: KB
authors.lastname: Russell
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ambrose
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Soll
authors.affiliation: Department of Molecular Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Bossler
authors.affiliation: Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA United States of America.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Milhem
authors.affiliation: Mercy Hospital System of Des Moines, Des Moines, IA United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Goldman
authors.affiliation: Developmental Studies Hybridoma Bank, Department of Biology, University of Iowa, Iowa City, IA United States of America.
authors.forename: David R
authors.identifier: http://orcid.org/0000-0002-5059-0315
authors.initials: DR
authors.lastname: Soll
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015415:Biomarkers; D002448:Cell Adhesion; D002460:Cell Line; D058948:Cell Tracking; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D004338:Drug Combinations; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen