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Abstract
The formation of distant metastases often determines the fate of patients with head and neck squamous cell carcinoma (HNSCC). The expression of cell adhesion molecules (CAMs) and their ligands of the leukocyte adhesion cascade has been associated with metastatic competence in several malignant entities. In this study, human HNSCC cell lines were analyzed in vitro and in a spontaneous metastatic xenograft model. Immunohistochemical analyses of several CAMs were performed on xenograft tumors and tissue microarrays (TMA) from 453 patients with head and neck squamous cell carcinomas with full histo-pathological and clinical follow-up data. UTSCC 24A and 24B cells bind to E-selectin in vitro, show E-selectin dependent binding to human umbilical vein endothelial cells (HUVECs), and express sLeX. All HNSCC cells engrafted into severe combined immunodeficient (SCID) mice, and UTSCC 24A cells formed sporadically spontaneous lung metastases. The expression of CAMs varied between the cell lines, but a correlation between tumor growth and metastatic potential did not exist. None of the CAMS or their ligands could be identified to be of prognostic relevance in the TMA study. The in vitro results indicate that E-selectin and sLeX are involved in the adhesion of HNSCC cells to endothelium. However, specific prognostic markers chosen from the leukocyte adhesion cascade for HNSCC were not identified.
Highlights
Improvement in the clinical management of head and neck squamous cell carcinoma (HNSCC)patients has resulted in loco-regional control of the primary tumor; long-term survival has not significantly changed due to the formation of distant metastases [1]
ITGA6, ITGB1, CD46, EpCAM, ALCAM, ITGAV, ITGB4, E-cadherin, and CD44 were detected on all analyzed HNSCC cells, without considerable differences between the cell lines
ICAM expression was highest on UTSCC 24A (1057 mean fluorescence intensity (MFI)), followed by UTSCC 24B (444 MFI) and Carey 24 (366 MFI) cells, whilst UTSCC
Summary
Improvement in the clinical management of head and neck squamous cell carcinoma (HNSCC)patients has resulted in loco-regional control of the primary tumor; long-term survival has not significantly changed due to the formation of distant metastases [1]. The downregulation of homotypic cell-cell adhesion is required for the detachment of metastatic cells from the primary tumor, while the upregulation of cell adhesion molecules (CAM) mediating the attachment of cancer cells to endothelial cells is a precondition for extravasation at the future metastatic site Regarding this step, it is assumed that tumor cells mimic mechanisms used by leukocytes and platelets in inflammatory processes. The initially loose adhesion causes integrin activation and full arrest of the cells to activated endothelial cells and is followed by the last step of the cascade, the transendothelial migration (TEM) [3,8,9,10] Though it is controversial whether selectin mediated rolling is necessary for the TEM of cancer cells and molecular mechanisms of leukocyte and tumor cell extravasation can differ, CAMs mediating the contact with endothelial cells are potentially the same [11,12]. Recent studies have reported that selectins and integrins play a role in the formation of metastases of various cancer types [11,13,14]
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