Abstract Title

Do Bacterial Pathogen Associated Molecular Patterns Promote Oral Cancer Cell Invasiveness? Literature Review, Preliminary Data, and Proposal of the Experiments

Lead Author Affiliation

1Doctor of Dental Surgery Program

Lead Author Status

DDS Year 2

Expected Graduation Date

2020

Presentation Category

Research, Literature Review

Introduction/Context/Diagnosis

The role of chronic inflammation for the cancer development was first described in 1863. Inflammation is also linked to invasion or metastasis of cancer. Inflammatory cytokines produced by local cells, in particular, tumor-associated macrophages, have long been known to increase metastasis. In addition, certain types of cancer cell secrete molecules promoting invasion and/or metastasis in response to bacterial virulence factors The oral cavity harbors a diverse and complex microbial community. The oral microbial flora contains approximately 700 species, and is composed of both commensal and pathogenic species. Bacteria accumulate on both the hard and soft tissues in a sessile biofilm. In this highly antigenic environment, oral mucosal tissue must maintain tolerance to commensal bacteria and to other molecules, such as food proteins in food. Under certain circumstances, however, the oral bacterial flora can induce an immune response resulting in inflammatory manifestations that can potentially trigger a development and progression of oral cancer. A striking association between periodontopathic pathogen and pancreatic cancer has been demonstrated, however, little is known about the relationship between effects of bacterial virulent factors on oral squamous cell carcinoma (OSCC) progression. The purpose of this proposed study is to examine how bacterial pathogen associated molecular patterns regulate the biological aspects of oral cancer cells

Methods/Treatment Plan

Pubmed search was conducted for literature search. To generate preliminary data, OSCC cell lines were cultured and stimulated with LPS, PGN, and flagellin for 24 hrs. Supernatent was collected for MMP-9 ELISA. Non-stimulated cells were processed for flow cytometric analysis of TLRs expression.

Results/Outcome

LITERATURE REVIEW

Toll-like receptor (TLR)-mediated signaling is implicated in cancer cell invasion, survival, and metastasis in a variety of cancers. For example, two breast cancer cell lines up-regulated TLR4, and matrix metaloproteinases (MMPs)-2 and 9 in response to lipopolysaccharide (LPS). Peptidoglycan (PGN), know TLR2 ligand, also enhanced invasiveness and adhesiveness of these cell lines. In addition, LPS induced biphasic phosphorylation of epidermal growth factor receptor (EGFR) in human biliary carcinoma cell lines. Immunohistochemical study confirmed expression of TLR‐2, TLR‐4, and TLR‐9 in primary OSCC, neck metastases as well as in recurrent OSCC.

PRELIMINARY DATA

All OSCC cell lines tested expressed functional TLRs 2, 4, and 5. HSC-3 also expressed EGFR. LPS was the most potent for HSC-3 and HSC-4 cells to induce MMP-9, while flagellin was the most potent MMP-9 inducer for HSC-2 cells. PGN did not have significant effect on MMP-9 secretion for all cells tested. However, it enhanced proliferation of both HSC-3 and HSC-4 cells.

Significance/Conclusions

Ligation of TLRs expressed on OSCC cell lines by their cognate ligands resulted in the cell proliferation and up-regulation of MMP-9 that plays a role in cancer invasion.

Our preliminary data is consistent with the roles of TLR ligands for enhanced cancer cell behavior observed in other cancer cell lines.

In this presentation, we will propose some experiments to test our two hypotheses:

1) TLR4 agonist LPS has pro-tumoral (progressive) effects on OSCC cell lines.

2) LPS (and/or other TLR ligands) challenge on OSCC cell lines results in sustained EGFR activation.

Comments/Acknowledgements

AS and EL contributed equally to this work.

Format

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Do Bacterial Pathogen Associated Molecular Patterns Promote Oral Cancer Cell Invasiveness? Literature Review, Preliminary Data, and Proposal of the Experiments

The role of chronic inflammation for the cancer development was first described in 1863. Inflammation is also linked to invasion or metastasis of cancer. Inflammatory cytokines produced by local cells, in particular, tumor-associated macrophages, have long been known to increase metastasis. In addition, certain types of cancer cell secrete molecules promoting invasion and/or metastasis in response to bacterial virulence factors The oral cavity harbors a diverse and complex microbial community. The oral microbial flora contains approximately 700 species, and is composed of both commensal and pathogenic species. Bacteria accumulate on both the hard and soft tissues in a sessile biofilm. In this highly antigenic environment, oral mucosal tissue must maintain tolerance to commensal bacteria and to other molecules, such as food proteins in food. Under certain circumstances, however, the oral bacterial flora can induce an immune response resulting in inflammatory manifestations that can potentially trigger a development and progression of oral cancer. A striking association between periodontopathic pathogen and pancreatic cancer has been demonstrated, however, little is known about the relationship between effects of bacterial virulent factors on oral squamous cell carcinoma (OSCC) progression. The purpose of this proposed study is to examine how bacterial pathogen associated molecular patterns regulate the biological aspects of oral cancer cells