Biology subjects

Kansal, V.

Publications and source records attributed to Kansal, V..

3 recordsLinked to original sources

bioRxiv2024

Orthotopic injection of an established syngeneic mouse oral cancer cell line (MOC1) induces a robust draining lymph node response

BackgroundPreclinical models are invaluable for studies on the pathogenesis and treatment of head and neck cancer. In recent years, there has been growing interest in the use of orthotopic syngeneic models, wherein head and neck cancer cell lines are injected into the oral cavity of immunocompetent mice. However, few such orthotopic models have been described in detail. In this brief report, we describe techniques for injection of mouse oral cancer 1 (MOC1) cells into the buccal mucosa and illustrate the tumor growth pattern, lymph node response, and changes in the tumor immune microenvironment over time. MethodsMOC1 cells were injected into the buccal mucosa of C57BL6 mice. Animals were sacrificed at 7, 14, 21, or 27 days. Tumors and lymph nodes were harvested and analyzed for immune cell subsets by flow cytometry. ResultsAll inoculated mice developed palpable buccal tumors by day 7 and required euthanasia for tumor burden and/or weight loss by day 27. Lymph node mapping showed that these tumors reliably drain to a submandibular lymph node, which enlarges considerably over time. As in MOC1 tumors in the flank, the proportion of intratumoral CD8+ T cells decreased over time, while neutrophilic myeloid cells increased dramatically. However, the pattern and time course of immune changes in the TME were slightly different in the orthotopic buccal model. ConclusionsWhen used orthotopically in the buccal mucosa, the MOC1 model induces a robust lymph node response and distinct pattern of immune cell infiltration, with peak immune infiltration by day 14.

cancer biology↗

bioRxiv2023

Inhibition of miR-214 expression by small molecules alleviates head and neck cancer metastasis by targeting ALCAM/TFAP2 signaling.

Predominantly, head and neck cancer (HNC) is considered a regional disease and develops in the nasal cavity, oral cavity, tongue, pharynx, and larynx. In the advanced stage, the HNC spread into distant organs. By the time head and neck cancer diagnosed, the estimated metastasis is occurred in 10-40% cases. The most important vital organs affected by distant metastasis are the lungs, bones, and liver. Despite several advancements in chemotherapies, no significant changes are observed as 5-year survival rate remains the same. Therefore, it is crucial to decipher molecular mechanisms contributing to the metastatic dissemination of head and neck cancer. Here, we tested a novel ALCAM/TFAP2 signaling by targeting multidisciplinary miR-214 expression in head and cancer cells. Our results revealed that HNC cell lines (CAL27, SCC-9, SCC-4, and SCC-25) exhibit higher expression of miR-214 compared with normal human bronchial epithelial (NHBE) cells. Higher expression of miR-214 drives the invasive potential of these cell lines. Down-regulation of miR-214 in CAL27 and SCC-9 cells either using an anti-miR-214 inhibitor (50nM) or a small molecule of green tea (EGCG) inhibited cell invasion. Treating CAL27 and SCC-9 cells with EGCG also reduces ALCAM expression, a key activated leukocyte cell adhesion molecule, potentially blocking mesenchymal phenotype. Dietary administration of EGCG significantly inhibits distant metastasis of SCC-9 cells into the lungs, liver, and kidneys. Our results also demonstrate that the reduction of miR-214 expression influences in vitro cell movement and extravasation, as evident by reduced CD31 expression, a neovascularization marker. Together, these studies suggest that identifying bioactive molecules that can inhibit distant metastasis regulated by the miRNAs may provide potent interventional approaches and a better understanding of the complex functions of miRNAs and their therapeutic targets for clinical application.

cancer biology↗

bioRxiv2023

Differentially deregulated microRNAs contribute to ultraviolet radiation-induced photocarcinogenesis through immunomodulation: An-analysis of microRNAs expression profiling.

MicroRNAs (miRNAs) are short non-coding RNA molecules (18-25 nucleotides) that regulate several fundamental biological processes. Emerging evidence has shown more than 1500 miRNAs functions in the cell cycle, proliferation, apoptosis, oxidative stress, immune response, DNA damage, and epigenetics alterations. miRNAs are bidirectionally in nature and act as a tumor suppressor and as an oncogene through crosstalk between tumor cells and immune cells. Although the roles of miRNAs in several cancers are well studied, little is known about ultraviolet B (UVB) radiation-induced skin cancer. Here, we performed a comprehensive screening of 1281 miRNAs in tumor tissues and compared their expression with normal skin. Our results demonstrate that the expression levels of 587 miRNAs were altered in tumor tissues compared to their expression in normal skin. The expression of 337 miRNAs was upregulated from 1.5-12 folds, while the expression of 250 miRNAs was downregulated up to 1.5-10 folds in tumors. Further, intraperitoneal injection of a mimic of down-regulated miR-15b (30nM) and an inhibitor of upregulated miR-133a (20nM) protect UVB-induced suppression of contact hypersensitivity (CHS) response. In conclusion, we identified a network of altered miRNAs in tumors that can serve as prognostic biomarkers and therapeutic targets to manage photocarcinogenesis effectively.

cancer biology↗