IN VITRO AND IN VIVO STUDY OF MELANOMA TUMOR CELL INVASION AND METASTASIS.

Persistent Link:
http://hdl.handle.net/10150/188148
Title:
IN VITRO AND IN VIVO STUDY OF MELANOMA TUMOR CELL INVASION AND METASTASIS.
Author:
GEHLSEN, KURT RONALD.
Issue Date:
1986
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The correlation of information obtained from in vitro investigations and in vivo experiments has frequently evaded researchers, especially in the area of tumor cell invasion and metastasis. In order to better understand and associate in vitro tumor cell invasion through basement membranes with in vivo tumor metastasis in syngeneic animal models, and the subsequent modulation of these processes, the following studies have been undertaken. Malignant murine melanoma cell lines designated B16F1 and B16F10, syngeneic to the C57BL6 mouse, a melanotic variant of the Cloudman S-91 melanoma cell line (denoted Mel-11a) with the syngeneic host being the DBA/2J mouse, and a malignant human melanoma line referenced as A375P (parental) and A375M (metastatic) were used for this dissertation project. Tumor cells were labeled with either ¹⁴C-thymidine or ¹²⁵I-deoxyuridine using previously established protocols. Radiolabeled tumor cells were introduced into the Membrane Invasion Culture System (MICS) in vitro, a system developed in our lab, and concomitantly into the lateral tail vein by injection or intracutaneously into the appropriate syngeneic host in the presence or absence of such biological response modifying agents as [Nle⁴, D-Phe⁷]-MSH, and α-MSH. The superpotent analogue of α-MSH ([Nle⁴, D-Phe⁷] -MSH) showed a proliferative and survival enhancing effect on tumor metastasis in vivo with no effect on in vitro tumor cell invasion, with similar effects demonstrated by α-MSH. The effects of these melanotropins on spontaneous metastasis formation appears to be negligible. The A375M and A375P human melanoma cells parallel their metastatic profile in vitro when assayed in MICS. In concert with these studies, the development of a control cell line, comprised of neural crest-derived melanocytes, and the study of their subsequent invasiveness in vitro were pursued. The neural crest-derived melanocytes were unable to invade the basement membranes (BM); although co-culturing neural crest cells with B16F10 melanoma cells produced an effect such that the neural crest cells did significantly invade the BMs. These studies demonstrate the ability of the MICS in vitro invasion assay to discriminate between tumor cells with differing metastatic propensities and could possibly be used in future studies to predict the effectiveness of biological response modifying agents in vivo.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Cancer invasiveness.; Metastasis.; Melanoma.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Philosophy; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Hendrix, J. C.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleIN VITRO AND IN VIVO STUDY OF MELANOMA TUMOR CELL INVASION AND METASTASIS.en_US
dc.creatorGEHLSEN, KURT RONALD.en_US
dc.contributor.authorGEHLSEN, KURT RONALD.en_US
dc.date.issued1986en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe correlation of information obtained from in vitro investigations and in vivo experiments has frequently evaded researchers, especially in the area of tumor cell invasion and metastasis. In order to better understand and associate in vitro tumor cell invasion through basement membranes with in vivo tumor metastasis in syngeneic animal models, and the subsequent modulation of these processes, the following studies have been undertaken. Malignant murine melanoma cell lines designated B16F1 and B16F10, syngeneic to the C57BL6 mouse, a melanotic variant of the Cloudman S-91 melanoma cell line (denoted Mel-11a) with the syngeneic host being the DBA/2J mouse, and a malignant human melanoma line referenced as A375P (parental) and A375M (metastatic) were used for this dissertation project. Tumor cells were labeled with either ¹⁴C-thymidine or ¹²⁵I-deoxyuridine using previously established protocols. Radiolabeled tumor cells were introduced into the Membrane Invasion Culture System (MICS) in vitro, a system developed in our lab, and concomitantly into the lateral tail vein by injection or intracutaneously into the appropriate syngeneic host in the presence or absence of such biological response modifying agents as [Nle⁴, D-Phe⁷]-MSH, and α-MSH. The superpotent analogue of α-MSH ([Nle⁴, D-Phe⁷] -MSH) showed a proliferative and survival enhancing effect on tumor metastasis in vivo with no effect on in vitro tumor cell invasion, with similar effects demonstrated by α-MSH. The effects of these melanotropins on spontaneous metastasis formation appears to be negligible. The A375M and A375P human melanoma cells parallel their metastatic profile in vitro when assayed in MICS. In concert with these studies, the development of a control cell line, comprised of neural crest-derived melanocytes, and the study of their subsequent invasiveness in vitro were pursued. The neural crest-derived melanocytes were unable to invade the basement membranes (BM); although co-culturing neural crest cells with B16F10 melanoma cells produced an effect such that the neural crest cells did significantly invade the BMs. These studies demonstrate the ability of the MICS in vitro invasion assay to discriminate between tumor cells with differing metastatic propensities and could possibly be used in future studies to predict the effectiveness of biological response modifying agents in vivo.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectCancer invasiveness.en_US
dc.subjectMetastasis.en_US
dc.subjectMelanoma.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhilosophyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorHendrix, J. C.en_US
dc.identifier.proquest8613432en_US
dc.identifier.oclc697515371en_US
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