Immunohistochemical analysis of integrins αvβ3, αvβ5 and α5β1, and their ligands, fibrinogen, fibronectin, osteopontin and vitronectin, in frozen sections of human oral head and neck squamous cell carcinomas

Abstract

Abstract. integrins mediate the interaction of cells with the extracellular matrix and are believed to be involved in tumor cell survival and metastasis, and in tumor angiogenesis. We used immunohistochemistry of fresh-frozen human tumor tissues to analyze the presence of integrins αvβ3, αvβ5 and α5β1, which are believed to be involved in tumor growth and migration, together with integrin ligands, vitronectin, osteopontin, fibronectin and fibrinogen, in human oral squamous cell carcinomas. Samples of squamous cell carcinomas and control tissues from patients without cancer undergoing oral or maxillofacial surgery were frozen in liquid nitrogen within 30 min of removal. Frozen sections were prepared, and the presence of integrins or ligands was visualized using standard immunohistochemistry (apaap) with a blinded evaluation. comparison of samples from the 40 oral cancer patients and the 20 controls revealed increased staining in tumors compared with the controls, and staining was demonstrated for αvβ3 in endothelia. αvβ5 staining was increased in the tumor samples, but this was associated with increased expression in stroma rather than in endothelia. modestly increased expression of α5β1 was observed in the tumor samples, and this was associated with tumor cells, endothelia and stroma. Expression of ligands for the integrins varied between tissue types, with increased fibrinogen and fibronectin expression in tumor endothelia. Confirmation of the presence of these integrins and their association with tumor cells, endothelia or stroma suggests their potential for these integrins in human oral tumors. Overall, the increased expression of integrins within tumors, particularly expression associated with endothelial cells, supports the principle of selective integrin blockade as a novel anticancer strategy. IntroductionWorldwide, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (HNSCC) has not significantly increased for many years (1-5). HNSCC is diagnosed predominantly at the age range of 50-70 years, but is also observed in younger patients (6-8). despite aggressive initial management of the primary tumor, locoregional recurrence occurs in some 60% of cases, and distant metastasis is observed in some 25%. therefore, innovative therapeutic concepts are urgently required.angiogenesis is essential for tumor progression and metastasis. tumor angiogenesis is complex and involves crosstalk between tumor-derived growth factors, the modified extracellular matrix that develops around tumors, and endothelial receptors for extracellular matrix and growth factors (9,10). inhibition of angiogenesis often suppresses the tumor growth of model tumors, and the suppression and eradication of malignant tumors by targeting angiogenetic endothelial cells is a rapidly evolving approach to cancer therapy (10,11

Fibronectin-guided migration of carcinoma collectives

“…FN (secreted or assembled) was undetectable in a set of HNSCC lines (Fig. 1e), consistent with the observed restriction of FN expression to stromal cells in the majority of these tumours, and in line with previous reports19.…”

“…As shown in Fig. 5a, αvβ3 integrin is not expressed by these cells, consistent with its expression in the endothelial rather than epithelial cells of these tumours19. Moreover, the use of αvβ5 blocking antibody had no impact on collective migration speed or directionality (Fig.…”

Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC

“…One of the most important targets of fluorescent probes in oncology is avß3 integrin, which shows large expression in neovessels and certain tumors, including HNSCC [1][2][3]. It plays an important role in angiogenesis, cell proliferation and migration and metastasis.…”

“…It requires fluorescent probes that specifically target cancer cells. One of the most important targets is ˛vß3 integrin, which is widely expressed on the surface of tumor-vessel endothelial cells and by most tumor cells, including HNSCC, during migration or by cells located on invasion frontlines [1][2][3]. Previous studies showed that near-infrared fluorescence imaging targeting ␣vß3 integrin provides benefit in HNSCC surgery by improving resection quality through the detection of tumor residue within the surgical bed that would be invisible to the naked eye even under magnifying lenses, so that the residue would be overlooked in purely macroscopically guided resection.…”

Emerging Strategies against Head & Neck Cancer – A Review

“…[1] Though diagnostic techniques have improved over the ages, yet the survival rates remain to be poor and have been the same in the last few years, with a 5-year survival rate of only 50% cases in oral squamous cell carcinoma (OSCC) from the time of diagnosis. [2] The disease shall progress at its own pace and continue to pose as a threat. So, we need to think beyond our present domains and make efforts in the regard.…”