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DTSTART;TZID=America/New_York:20260630T100000
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URL;TYPE=URI:https://www.wpi.edu/news/calendar/events/bme-ms-thesis-defense
 -jaya-mills-effects-matrix-stiffness-cell-morphology-and-expression-lympha
 tic
SUMMARY:BME MS Thesis Defense: Jaya Mills “Effects of Matrix Stiffness on C
 ell Morphology and Expression of Lymphatic Adhesion Molecules in PANC-1 Pa
 ncreatic Ductal Adenocarcinoma Cells”
LOCATION:United States
DESCRIPTION:\n\n\n      \n      \n\n\n\nMaster’s Thesis Defense\n\n“Effects
  of Matrix Stiffness on Cell Morphology and Expression of Lymphatic Adhesi
 on Molecules in PANC-1 Pancreatic Ductal Adenocarcinoma Cells”\nJaya Mills
 \nAbstract: With a five-year survival rate of ~13.7%, Pancreatic Ductal Ad
 enocarcinoma (PDAC) is on track to become the second most deadly cancer wi
 thin five years. Higher mortality results, in large part, to the majority 
 of PDAC patients being diagnosed with some degree of tumor cell invasion w
 hich includes metastasis to the lymph nodes and distant organs facilitated
  by lymphatic vasculature. PDAC exhibits desmoplastic changes in the tumor
  tissue that can promote dense fibrosis around the tumor and contribute to
  epithelial-to-mesenchymal transition (EMT), a sign of metastatic disease 
 progression. Since PDAC is characterized by its dense extracellular matrix
  (ECM) with a confined ECM microstructure, it is important to understand t
 he disease within the context of these factors. There is a general lack of
  in vitro PDAC models that account for these ECM changes at a pathological
  level, and even fewer models investigate desmoplastic effects on tumor ce
 ll features that relate to lymphatic metastasis. This research aims to cha
 racterize and leverage an in vitro 3D tumor model for assessing changes in
  PDAC cell morphology and expression of cell adhesion markers involved in 
 lymphatic trafficking during metastasis. Our lab uses methacrylated type I
  collagen with photo-crosslinking (PhotoCol®) to tune collagen properties 
 to reflect normal and tumor tissue stiffness, and PANC-1 cells (commercial
  PDAC cell line) are used as a tumor cell population with metastatic poten
 tial. Biophysical properties of PhotoCol®, such as stiffness and microstru
 cture (confinement), were evaluated via rheology (shear storage modulus) a
 nd confocal microscopy (fibril area fraction). The effects of ECM stiffnes
 s and confinement on PANC-1 morphology (compactness, eccentricity, form fa
 ctor) and expression of lymphatic trafficking markers (CCR7 and CXCR4) wer
 e evaluated via fluorescent microscopy and western blotting, respectively.
  Results showed that 8 mg/mL and 3 mg/mL PhotoCol® formulations could repr
 esent pancreatic tissues within the ranges of early tumor ECM (high stiffn
 ess, high confinement) and normal ECM (low stiffness, low confinement), re
 spectively. In the lower stiffness and confinement condition, PANC-1 cells
  exhibited more of a protrusive mesenchymal phenotype (higher compactness 
 and eccentricity; lower form factor) that typically signals potential EMT 
 behavior. Conversely, cells in stiffer, more confined matrices had a more 
 rounded morphology. While the latter result does not have characteristic E
 MT behavior, it could suggest that cells were not transitioning, or they w
 ere undergoing an alternative or secondary transition that is known to occ
 ur in solid tumors. When evaluating lymphatic trafficking markers, CXCR4 a
 nd CCR7, western blot results showed that CXCR4 expression increased in th
 e high stiffness and confinement condition, while CCR7 expression decrease
 d. Studies have shown that CCR7 is directly related to lymph node metastas
 is, while CXCR4 is more associated with broad tissue lymphatics and the de
 smoplastic PDAC microenvironment. This result suggests a more dominant rol
 e for stiffness in CXCR4 expression compared to CCR7 and a higher likeliho
 od of metastasis occurring in stiffer conditions via lymphatic vasculature
  directly surrounding PDAC tumors and in distant organs. However, it does 
 not necessarily show correlation between stiffness and metastatic events a
 t the lymph node specifically. Overall, this research shows the importance
  of studying the effects of ECM stiffening and confinement on PDAC progres
 sion and metastasis and leverages PhotoCol® as a tunable matrix material f
 or an in vitro PDAC model.  \n\n\n\n\nThesis Advisor:\nDefense Committee:\
 n\n\n\n\nCatherine Whittington, PhD\nAssociate Professor\nBiomedical Engin
 eering\nWorcester Polytechnic Institute\n\n\nGeorge Pins PhD (Chair)\nProf
 essor\nBiomedical Engineering\nWorcester Polytechnic Institute\n\n\nAmity 
 Manning, PhD\nProfessor\nBiology \& Biotechnology\nWorcester Polytechnic I
 nstitute\n\n\n\n\nFor a zoom link, please email kharrison@wpi.edu\n
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