<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process"^^ . "The cell-cell and cell-matrix adhesion molecule CD44 and its numerous splice variants are involved in a multitude of physiological and pathological processes, including tumour progression. Especially variant CD44 has been implicated in metastasis formation. For long term in vivo experiments on metastasis formation, a plasmid based RNAi technique was applied to generate stable splice variant ‘v7’-specific CD44 knock-down clones of a highly metastatic rat pancreatic adenocarcinoma cell line (BSp73ASML). The resulting phenotype was characterized with an emphasis on interactions of CD44v with the tumour surrounding during the course of metastasis formation. Loss of CD44v is accompanied in vivo by a marked reduction in metastatic growth in the lymph nodes and particularly in the lung, which could be reverted by restoring CD44v expression in the knock-down cells. The impaired metastatic growth was not due to a lower proliferative activity or a reduced anchorage-independence of these cells in vitro. Instead, they display several defects, which can be attributed to perturbed interactions of CD44v with the microenvironment. Compared to ASMLwt cells CD44vk.d. cells do not form cell aggregates in stromal surroundings, such as lymph nodes and the lung, due to lost cell-cell adhesion, mediated by interactions of CD44v and hyaluronic acid (HA). Furthermore, CD44vk.d. cells exhibit an impaired matrix production, as CD44v is most likely involved in the assembly of matrix components, containing HA, collagen and laminin. The matrix supports rapid adhesion of ASML cells through ?1 integrin and in addition contributes to survival. Finally, the loss of CD44v is accompanied by a marked decrease in apoptosis resistance. Impaired PI3K-Akt survival signalling, activated by CD44v was identified as the cause of this defect. In conclusion, CD44v contributes to the metastatic phenotype of ASML cells as a multifunctional player interacting with the surrounding in several ways. First, as cell-cell adhesion molecule by mediating cell aggregation, second, as cell-matrix adhesion molecule by organizing matrix generation and last, as signalling molecule supporting survival. This highlights the role of variant CD44 in the metastatic spread of tumour cells through complex interactions with the tumour microenvironment and underlines the important role of a highly regulated interplay between tumour cells and their surrounding for metastasis formation. "^^ . "2006" . . . . . . . . "Pamela"^^ . "Klingbeil"^^ . "Pamela Klingbeil"^^ . . . . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (PDF)"^^ . . . "Isoform_specific_Loss_of_CD44_Interferes_with_Different_Aspe.pdf"^^ . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Isoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #7292 \n\nIsoform-specific Loss of CD44 Interferes with Different Aspects of the Metastatic Process\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .