In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. RESULTS: Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. CONCLUSION: The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms

Socioeconomic and living conditions are determinants of hip fracture incidence and age occurrence among community-dwelling elderly

Summary: In this prospective, 10-year study in community-dwelling elderly aged 50years and over, hip fracture incidence and accordingly age at hip fracture were inversely associated with the area-level income, independently of the geographical area. Age at hip fracture also depended of marital status but in a gender-specific way. Purpose: The purpose of this study is to investigate the impact of socioeconomic and living conditions on hip fracture incidence and age occurrence among community-dwelling elderly. Method: Between January 1991 and December 2000, 2,454 hip fractures were recorded in community-dwelling adults aged 50years and over in the Geneva University Hospital, State of Geneva, Switzerland. Median annual household income by postal code of residence (referred to as area-level income) based on the 1990 Census was used as a measure of socioeconomic condition and was stratified into tertiles (<53,170; 53,170-58,678; and ≥58,678 CHF). Hip fracture incidence and age occurrence were calculated according to area-level income categories and adjusted for confounding factors among community-dwelling elderly. Results: Independently of the geographical area (urban versus rural), community-dwelling persons residing in areas with the medium income category presented a lower hip fracture incidence [OR 0.91 (0.82-0.99), p = 0.049] compared to those from the lowest income category. Those in the highest income category had a hip fracture at a significant older age [+1.58 (0.55-2.61) year, p = 0.003] as compared to those in the lowest income category. Age at hip fracture also depended on marital status but in a gender-specific way, with married women fracturing earlier. Conclusions: These results indicate that incidence and age occurrence of hip fracture are influenced by area-level income and living conditions among community-dwelling elderly. Prevention programs may be encouraged in priority in communities with low incom

Reversal of the hip fracture secular trend is related to a decrease in the incidence in institution-dwelling elderly women

Summary: In this prospective 10-year study in elderly aged 60years and over, there was a 1.3% per year reduction in the standardized incidence of hip fracture in women but not in men. This decrease was mainly due to changes in the standardized incidence of hip fracture in institution-dwelling women. Introduction: A decrease in age-adjusted hip fracture incidence has been recently demonstrated in some countries. Since a large proportion of hip fractures occur in nursing homes, we analyzed whether this decreasing trend would be more detectable in institution-dwelling elderly compared with community-dwelling elderly. Methods: All hip fracture patients aged 60years and over were identified in a well-defined area. Incidence of hip fracture, age- and sex-adjusted to the 2000 Geneva population, was computed in community- and institution-dwelling elderly. Results: From 1991 to 2000, 1,624 (41%) hip fractures were recorded in institutionalized-dwelling elderly and 2,327 (59%) in community-dwelling elderly. The standardized fracture incidence decreased by 1.3% per year in women (p = 0.039), but remained unchanged in men (+0.5%; p = 0.686). Among institution-dwelling women, hip fracture incidence fell by 1.9% per year (p = 0.044), whereas it remained stable among community-dwelling women (+0.0%, p = 0.978). In men, no significant change in hip fracture incidence occurred among institution- or community-dwelling elderly. Conclusions: The decrease in the standardized hip fracture incidence in institution-dwelling women is responsible for the reversal in secular trend. Future research should include stratification according to the residential status to better identify the causes responsible for the trend in hip fracture incidenc