Skeletal manifestations of Marfan syndrome associated to heterozygous R2726W FBN1 variant: sibling case report and literature review.

BACKGROUND: FBN1 (15q21.1) encodes fibrillin-1, a large glycoprotein which is a major component of microfibrils that are widely distributed in structural elements of elastic and non-elastic tissues. FBN1 variants are responsible for the related connective tissue disorders, grouped under the generic term of type-1 fibrillinopathies, which include Marfan syndrome (MFS), MASS syndrome (Mitral valve prolapse, Aortic enlargement, Skin and Skeletal findings, Acromicric dysplasia, Familial ectopia lentis, Geleophysic dysplasia 2, Stiff skin syndrome, and dominant Weill-Marchesani syndrome. CASE PRESENTATION: Two siblings presented with isolated skeletal manifestations of MFS, including severe pectus excavatum, elongated face, scoliosis in one case, and absence of other clinical features according to Ghent criteria diagnosis, were screened for detection of variants in whole FBN1 gene (65 exons). Both individuals were heterozygous for the R2726W variant. This variant has been previously reported in association with some skeletal features of Marfan syndrome in the absence of both tall stature and non-skeletal features. These features are consistent with the presentation of the siblings reported here. CONCLUSION: The presented cases confirm that the R2726W FBN1 variant is associated with skeletal features of MFS in the absence of cardiac or ocular findings. These findings confirm that FBN1 variants are associated with a broad phenotypic spectrum and the value of sequencing in atypical cases.

Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A.

Extracellular vesicles (EVs) mediate many stages of tumor progression including angiogenesis, escape from immune surveillance, and extracellular matrix degradation. We studied whether EVs from plasma of women with breast cancer are able to induce an epithelial-mesenchymal transition (EMT) process in mammary epithelial cells MCF10A. Our findings demonstrate that EVs from plasma of breast cancer patients induce a downregulation of E-cadherin expression and an increase of vimentin and N-cadherin expression. Moreover, EVs induce migration and invasion, as well as an increase of NFκB-DNA binding activity and MMP-2 and MMP-9 secretions. In summary, our findings demonstrate, for the first time, that EVs from breast cancer patients induce an EMT-like process in human mammary non-tumorigenic epithelial cells MCF10A.

Elevated concentration of microvesicles isolated from peripheral blood in breast cancer patients.

BACKGROUND AND AIMS: Breast cancer is the most common cancer and the main cause of cancer deaths in women worldwide. Microvesicles (MVs) are fragments of the plasma membrane secreted from cytoplasmic membrane compartments by normal and malignant cells. An increase in MV number has been found in peripheral blood of patients with several diseases including cancer. We hypothesized that MV number and the relative amount of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) proteins in plasma fractions enriched in MVs and deprived of platelet-derived MVs are related to the presence of breast cancer. METHODS: Plasma fractions enriched in MVs and deprived of platelet-derived MVs were obtained by differential centrifugation of blood samples. MV number was evaluated by BD TruCOUNT Tubes (BD Biosciences). FAK and EGFR proteins were analyzed by Western blot. RESULTS: MV number in plasma fractions enriched with MVs and deprived of platelet-derived MVs is higher in breast cancer patients with stages I-IV as well as with T2-T4 tumors, in comparison to control group. In addition, plasma fractions enriched in MVs present FAK and EGFR proteins and their amount is increased in some stages of breast cancer in comparison to control group. CONCLUSIONS: Our findings strongly suggest that MV number and the amount of FAK and EGFR in plasma fractions enriched in MVs are associated with some stages of breast cancer.