BACKGROUND: Oral squamous cell carcinoma (OSCC) is a head and neck cancer that is typically diagnosed in elderly patients. Because the incidence rates of OSCC increases by two-to-four fold in older age groups, age is considered one of the major risk factors. With aging, there is an accumulation of mutational changes that may initiate tumor formation and a growing population of senescent cells that can reprogram the microenvironment via soluble factors. The result of these changes can create a tumor permissive microenvironment. Although age is considered a risk factor in OSCC, there have not been many preclinical studies on the role of aging in the oral microenvironment.
OBJECTIVE: To investigate the role of aging in modulating early oral lesions in the microenvironment by analyzing protein localization and alterations in cellular phenotypes.
METHODS: Tongue sections from non-treated 12-week-old, non-treated aging 31-week-old, and 4NQO-treated 31-week-old mice were subjected to immunohistochemical analyses (IHC). The sections were incubated with antibodies against anti-𝛼-SMA, -PDGFRβ and -E-cadherin to observe changes in cellular morphology, staining intensity, localization and frequency of appearance.
RESULTS: The membranous localization of E-cadherin significantly decreased from young and aging normal epithelia to severe dysplasia. 𝛼-SMA expression was observed in the cytoplasm and at the membrane of elongated and spindle-like epithelial cells in severe dysplasia. 𝛼-SMA and PDGFRβ expressions were localized to blood vessels/pericytes in the stroma for all tissue samples. In the stroma surrounding severe epithelial dysplasia, there was an increase in vascular structures. While no 𝛼-SMA-positive myofibroblasts were found in any of the stroma, PDGFRβ-positive stromal cells were found in the stroma of aging tissues from 4NQO-treated mice.
CONCLUSIONS: This study provides evidence that aging has a role in modulating the microenvironment in the early pre-cancerous lesions. The appearance of myofibroblasts may have originated from senescent cell populations and the effects of the 4NQO carcinogen caused changes in the expression and localization of E-cadherin, 𝛼-SMA and PDGFRβ as well as in cellular phenotypes. The changes observed in the precancerous lesions may contribute to their progression to OSCC.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43442 |
| Date | 22 November 2021 |
| Creators | Le, Amanda |
| Contributors | Kukuruzinska, Maria A., Stashenko, Phillip |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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