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Determination of the metastatic pote...
~
Burleson, Kathryn Maureen.
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Determination of the metastatic potential of ovarian carcinoma spheroids.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Determination of the metastatic potential of ovarian carcinoma spheroids./
Author:
Burleson, Kathryn Maureen.
Description:
152 p.
Notes:
Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4368.
Contained By:
Dissertation Abstracts International65-09B.
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3148331
ISBN:
0496068792
Determination of the metastatic potential of ovarian carcinoma spheroids.
Burleson, Kathryn Maureen.
Determination of the metastatic potential of ovarian carcinoma spheroids.
- 152 p.
Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4368.
Thesis (Ph.D.)--University of Minnesota, 2004.
This dissertation investigates the metastatic potential of ovarian carcinoma spheroids by evaluating their adhesive, migratory, and invasive properties. First, the adhesive ability of spheroids was established. Spheroids were generated from the NIH:OVCAR5 human ovarian cancer cell line or isolated from the ascites of eleven ovarian carcinoma patients. NIH:OVCAR5 spheroids adhered equally to laminin, fibronectin, type I collagen, and type IV collagen, while patient ascites spheroids adhered preferentially to type I collagen, hyaluronan, and fibronectin. This adhesion occurred primarily through the beta1 integrin subunit. Significantly, both NIH:OVCAR5 and ascites spheroids were also capable of adhering to live monolayers of human mesothelial cells via beta1 integrin interactions.
ISBN: 0496068792Subjects--Topical Terms:
1017686
Biology, Cell.
Determination of the metastatic potential of ovarian carcinoma spheroids.
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152 p.
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Source: Dissertation Abstracts International, Volume: 65-09, Section: B, page: 4368.
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Adviser: Amy P. N. Skubitz.
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Thesis (Ph.D.)--University of Minnesota, 2004.
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This dissertation investigates the metastatic potential of ovarian carcinoma spheroids by evaluating their adhesive, migratory, and invasive properties. First, the adhesive ability of spheroids was established. Spheroids were generated from the NIH:OVCAR5 human ovarian cancer cell line or isolated from the ascites of eleven ovarian carcinoma patients. NIH:OVCAR5 spheroids adhered equally to laminin, fibronectin, type I collagen, and type IV collagen, while patient ascites spheroids adhered preferentially to type I collagen, hyaluronan, and fibronectin. This adhesion occurred primarily through the beta1 integrin subunit. Significantly, both NIH:OVCAR5 and ascites spheroids were also capable of adhering to live monolayers of human mesothelial cells via beta1 integrin interactions.
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Next, NIH:OVCAR5 or ascites spheroids were plated on a variety of ECM components to determine their ability to disaggregate. NIH:OVCAR5 spheroids demonstrated a dramatic disaggregation on type I collagen within 24 hours, while laminin and type IV collagen stimulated minor cell migration. In general, patient ascites spheroids plated on ECM did not disaggregate, but increased in surface area approximately 2-fold within 24 hours on all ECM components tested. However, a small percentage of ascites spheroids completely disaggregated on type I collagen, indicating that individual patient spheroids may acquire an invasive phenotype.
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Subsequently, spheroid invasive ability was evaluated. NIH:OVCAR5 spheroids adhered to, disseminated on, and invaded into monolayers of live human mesothelial cells, rapidly establishing foci of invasion that increased in size 200-fold within a week. Blocking beta1 integrin interactions, matrix metalloproteinases, and serine proteases significantly inhibited spheroid invasion. Patient ascites spheroids in general did not invade, but adhered to and disseminated on the mesothelial cells and their exposed ECM. However, some ascites samples contained spheroids that showed a more malignant phenotype. These spheroids invaded into the mesothelial cell monolayers to establish proliferating foci, demonstrating the heterogeneity of the ascites cellular content and providing evidence that invasive subtypes exist.
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This research implicates ascites spheroids as a potential source of secondary tumor growth in ovarian carcinoma, which should be taken into consideration in the design of future therapeutics. Additionally, these studies provide valuable quantitative assays adaptable for studying spheroid biology in a broad range of diseases.
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School code: 0130.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3148331
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