Quantitative imaging-based analysis of cell state heterogeneity in Head and Neck Squamous Cell Carcinoma (HNSCC)

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http://urn.fi/URN:NBN:fi:hulib-202106303264
Title: Quantitative imaging-based analysis of cell state heterogeneity in Head and Neck Squamous Cell Carcinoma (HNSCC)
Author: Dawka, Sagarika
Contributor: University of Helsinki, Faculty of Biological and Environmental Sciences
Publisher: Helsingin yliopisto
Date: 2021
Language: eng
URI: http://urn.fi/URN:NBN:fi:hulib-202106303264
http://hdl.handle.net/10138/331993
Thesis level: master's thesis
Degree program: Genetiikan ja molekulaaristen biotieteiden maisteriohjelma
Master's Programme in Genetics and Molecular Biosciences
Magisterprogrammet i genetik och molekylära biovetenskaper
Specialisation: Solu- ja kehitysbiologia
Cell and Developmental Biology
Cell- och utvecklingsbiologi
Abstract: Head and neck squamous cell carcinoma (HNSCC) is a diverse group of cancers defined by their localization in the head and neck region. These cancers are recognized for the heterogeneity between tumors from separate patients (inter-patient heterogeneity) as well as between cell types within individual tumors (intra-tumoral heterogeneity). Heterogeneity poses a major clinical challenge by making accurate diagnosis and selection of treatment options difficult. This study aims to improve precision of prognosis, quantify heterogeneity in HNSCC, and address its functional implications using two approaches: (1) profiling a set of HNSCC patient tumors using multiplexed immunohistochemistry and single-cell computational methods to identify a set of phenotypic descriptors correlating with differences in survival; and (2) using patient-derived cancer cell lines to investigate which cellular features correlate with relevant functional properties such as plasticity, invasiveness, clonogenicity and tumorsphere-forming abilities of cells. Epithelial-mesenchymal transition (EMT) as well as excistence of stem cell like states have been implicated in cancer aggressiveness and poor outcomes. We thus focused on identification of putative EMT, partial EMT (pEMT) and stem cell-like states. Based on a combination of morphometric analyses and stem cell- and EMT marker profiling, our computational method assigned patients into groups with different survival probabilities, and these patients’ tumors were found to differ in their expression of the stem cell transcription factor Sox2, the EMT transcription factor Slug, and in their morphometric parameters. Functional studies of patient-derived cell lines found that significant differences exist in protein expression, morphological features and cell behaviours between cell lines in vitro, and that inhibiting EMT promotes clonogenicity and can increase Sox2 expression. Thus, this study highlights important heterogeneous patient phenotypes and cellular behaviours in HNSCC, and implicates the need for a multimodal approach to diagnosis and therapy of this cancer.
Subject: head and neck squamous cell carcinoma (HNSCC)
head and neck cancer
tumour heterogeneity
epithelial-mesenchymal transition (EMT)
partial EMT (pEMT)
nuclear mechanics
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