Werner W. Franke

Bio: Werner W. Franke is an academic researcher from German Cancer Research Center. The author has contributed to research in topics: Cytokeratin & Intermediate filament. The author has an hindex of 134, co-authored 561 publications receiving 58390 citations. Previous affiliations of Werner W. Franke include University of Freiburg.

Different intermediate-sized filaments distinguished by immunofluorescence microscopy

Abstract: The major protein of intermediate-sized filaments in mouse 3T3 cells, for which the name vimentin is proposed, has a molecular weight of 57,000. Antibodies against vimentin and antibodies against prekeratin have been used in parallel in immunofluorescence microscopy on a variety of cultured cells as well as on frozen tissue sections. Both antibodies decorate extended wavy arrays of filaments that are different from microfilaments and microtubules. Intermediate filament bundles decorated by antibodies against prekeratin are predominant in many epithelial cells, including epithelia-derived tumor cells, and are not decorated by antibodies to vimentin. In contrast, intermediate filaments decorated by antibodies against vimentin are widespread among nonmuscle cells of mesenchymal origin, including transformed cells, and also occur in other cells. Perinuclear whorls of aggregates of intermediate filaments induced by prolonged treatment with Colcemid generally show strong decoration with antibodies against vimentin. No significant reaction with either antiserum has been observed in muscle structures or in brain nerve tissue. These observations show that intermediate filaments with similar ultrastructure and solubility characteristics can be distinguished immunologically.

Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.

Abstract: The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20, whose expression is almost entirely confined to the gastric and intestinal epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs) specific for CK 20 were raised and characterized by applying immunoblotting and immunocytochemical screening. All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue samples. A total of 711 cases of primary and metastatic cancer, mostly carcinomas, were analyzed immunohistochemically for CK-20 expression, using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell carcinomas and frequently also in adenocarcinomas of the stomach, bile system, and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary, and small-cell lung carcinomas were essentially or completely negative. The authors propose to use CK 20 as a diagnostic marker valuable in distinguishing different types of carcinomas, notably when presenting as metastases.

Fibroblasts in cancer

Abstract: Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. Their production of growth factors, chemokines and extracellular matrix facilitates the angiogenic recruitment of endothelial cells and pericytes. Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

Abstract: Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.

Abstract: In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation-specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long-term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.

Wnt signalling in stem cells and cancer

Abstract: The canonical Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signalling has also been associated with cancer. This has raised the possibility that the tightly regulated self-renewal mediated by Wnt signalling in stem and progenitor cells is subverted in cancer cells to allow malignant proliferation. Insights gained from understanding how the Wnt pathway is integrally involved in both stem cell and cancer cell maintenance and growth in the intestinal, epidermal and haematopoietic systems may serve as a paradigm for understanding the dual nature of self-renewal signals.