Submitted Abstract:
The Solid Tumor Microenvironment: Physiological Biomarkers of Tumor Progression
Crawford, Sarah1
1Cancer Biology Research Laboratory, Biology Department, Southern Connecticut State university
Tumor micro-environmental components that drive cancer progression include: hypoxic interior associated with oxidative stress responses, inflammatory pathways critical to tumor survival, glycolysis and altered redox regulation of cell growth. Our research has shown that altered biophysical parameters of growth regulation may be associated with increased tumor vesicle production. These changes may be associated with altered calcium metabolism, as increased extracellular calcium was shown to affect tumor spheroid formation and enhance the production of tumor associated microvesicles. The microvesicles produced under these conditions appear to have an important role in tumor physiology, including: the morphological transformation of normal diploid fibroblasts, spheroid aggregate formation and cell-to-cell interactions and motility.
Additional research on the tumor microenvironment conducted in this laboratory indicates that serum depletion and/or increased glucose concentration favors tumor cell detachment from fibronection extracellular matrix and tumor spheroid formation.
A proposed model for the environmental impact on solid tumor biology involves a sequence of events that can be correlated to the classic initiation/ promotion/ progression model of tumorigenesis at the level of solid tumor biology:
· Hyperplastic growth associated with proliferative dysregulation results in disorganized tissue structural organization that affects tissue polarity and cell contact/attachment parameters.
· Tissue disorganization promotes solid tumor formation by abrogating normal cell contact attachment parameters that produce epigenetic effects on cell signal/transcription processes that contribute to epithelial-to-mesenchymal transitions of affected tissue.
· Cytoarchitectural disruption increases the production of TAMVs that elicit morphological transformation of stromal tissue by a processs the lab has termed “insertional membrane editing”. These changes further promote the formation of incipient solid tumors in situ, whose formation is in part mediated by extracellualar TAMVs.
Each of these biophysical parameters may serve as biomarkers for progressive changes in tumor physiology associated with disease progression.
We look forward to seeing you!
The ISREC 2011 Organizers
Doug Hanahan, Joerg Huelsken, Joachim Lingner, Melody Swartz, Erwin Wagner
0 comments:
Post a Comment