Caveolin-1 overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-ß catenins complex and multiple ErbB receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas.

The presence of lymph node metastases is one of the most important prognostic indicators in head and neck squamous cell carcinomas (HNSCCs). An alteration of the E-cadherin-catenins complex and EGFR is essential for the invasiveness of cancer cells. Caveolin-1, the major structural protein of the caveolae, represents a scaffolding molecule for several signaling proteins including EGFR. Although caveolin-1 has been shown to play a role in inducing the invasive phenotype of cancer cells, its role appears to be cell-type specific and for some tumors it has not been defined yet. In this study we used 57 HNSCC specimens to investigate whether the abnormal expression of caveolin-1 was associated with the derangement of the E-cadherin-catenins complex and with the overexpression of ErbB receptors. We demonstrate that in HNSCCs caveolin-1 overexpression is associated with the simultaneous abnormal expression of at least one member of the E-cadherin/α-ß catenins complex and multiple ErbB receptors as well as with lymph node metastases. We also demonstrate that chronic stimulation of a human hypopharyngeal carcinoma cell line (FaDu) with EGF induced the internalization of ß-catenin and caveolin-1 and their co-localization with EGFR. Moreover, EGF treatment induced an increased physical interaction between EGFR/ß-catenin/caveolin-1 and between E-cadherin/ß-catenin/caveolin-1. These molecular events were associated with an increased directional motility of FaDu cells in vitro. These findings may provide new insight into the biology of HNSCC progression and help to identify subgroups of primary HNSCCs with a more aggressive behavior.

Intercalated disk remodeling in delta-sarcoglycan-deficient hamsters fed with an alpha-linolenic acid-enriched diet.

Cardiomyocyte intercalated disks of delta-sarcoglycan-deficient cardiomyopathic hamsters (CMPHs) exhibit a pathological accumulation of the N-cadherin/catenin complex. CMPHs fed with an alpha-linolenic acid (ALA)-enriched diet (CMPH/FS) display an extended longevity compared to those fed with a standard diet (CMPH/PT) owing to, among others, the amelioration of both cardiac tissue structure and myocardial function. The present investigation was aimed at evaluating whether and to what extent the ALA-enriched diet affects the remodeling of CMPH cardiomyocyte intercalated disks and the expression of molecules, including N-cadherin, catenins and connexin 43 (CX43), involved in their organization. Western blot and immunohistochemical analysis demonstrated that the expression of N-cadherin, alpha- and beta-catenin is significantly reduced in cardiomyocyte intercalated disks of CMPH/FS vs. CMPH/PT and is lowered to levels similar to those found in healthy hamsters (GSH/PT), as well as transmission electron microscopy indicated that the cardiomyocyte intercalated disk ultrastructure is also re-established in CMPH/FS. In addition, the delocalization of CX43 as well as the presence of gap junctions were detectable at the lateral plasmamembrane of CMPH/FS cardiomyocytes, while the expression of myocardial CX43 was markedly reduced in both CMPH/PT and CMPH/FS, as compared to GSH/PT. Collectively, the present results demonstrate a substantial effect of an ALA-enriched diet on cardiomyocyte intercalated disk structure and molecular composition and further supports the beneficial effects of omega-3 polyunsaturated fatty acids in the prevention of potentially dangerous arrhythmias in cardiac diseases.

The ribosomal P0 protein induces a spontaneous immune response in patients with head and neck advanced stage carcinoma that is not dependent on its overexpression in carcinomas.

A typical feature in systemic lupus erythemathosus patients is the presence of autoantibodies to the carboxyl-terminal homologous P proteins (P0, P1, P2) domain (C-22 P0 epitope). In this report we provide evidence for the in vivo immunogenicity of the P0 protein in head and neck cancer patients as well as overexpression by immunohistochemistry of the C-22 P0 epitope in invasive carcinomas (55/57). Overexpression of this epitope was also significantly associated with a number of pathological lesions arising in the head and neck stratified epithelium including acanthosis (8/8), benign tumors (11/11), dysplasia (23/25) and in situ carcinomas (9/9). Intermediate cell layer restricted epitope overexpression was observed in well differentiated carcinomas, while undifferentiated tumors showed overexpression throughout the cell layers. Employing recombinant P proteins, sera from 40 of the 57 carcinoma patients and 39 normal donors, were subjected to immunoblot analysis. Immunity to P0 protein (7/40) was associated with malignancy and with advanced disease stage, but it was not dependent on the C-22 P0 epitope overexpression, although it was the preferential autoantibody target in 4 patients. Increased expression of the C-22 P0 epitope on the surface of pharynx cancer cells following cellular stress in vitro, may imply P0 protein presentation as an in vivo autoantibody target in cancer patients. Evidence for immunity to the P0 protein, as well as overexpression in patients with head and neck carcinoma may be relevant for monitoring cancer progression, in planning immunotherapeutic strategies, and contribute to the understanding of immuno-biological behaviour of head and neck carcinomas.