Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.

https://science.sciencemag.org/content/sci/267/5203/1449.full.pdf

The Fas Death Factor

Beneath the complexity and idiopathy of every cancer lies a limited number of 'mission critical' events that have propelled the tumour cell and its progeny into uncontrolled expansion and invasion One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression Adroit targeting of these critical events should have potent and specific therapeutic consequences

Proliferation, cell cycle and apoptosis in cancer

Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.

Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues; it also occurs in specific pathologic contexts. Morphologically, it involves rapid condensation and budding of the cell, with the formation of membrane-enclosed apoptotic bodies containing well-preserved organelles, which are phagocytosed and digested by nearby resident cells. There is no associated inflammation. A characteristic biochemical feature of the process is double-strand cleavage of nuclear DNA at the linker regions between nucleosomes leading to the production of oligonucleosomal fragments. In many, although not all of the circumstances in which apoptosis occurs, it is suppressed by inhibitors of messenger RNA and protein synthesis. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and it is increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. However, much of the current interest in the process stems from the discovery that it can be regulated by certain proto-oncogenes and the p53 tumor suppressor gene. Thus, c-myc expression has been shown to be involved in the initiation of apoptosis in some situations, and bcl-2 has emerged as a new type of proto-oncogene that inhibits apoptosis, rather than stimulating mitosis. In p53-negative tumor-derived cell lines transfected with wild-type p53, induction of the gene has, in rare cases, been found to cause extensive apoptosis, instead of growth arrest. Finally, the demonstration that antibodies against a cell-surface protein designated APO-1 or Fas can enhance apoptosis in some human lymphoid cell lines may have therapeutic implications.

Apoptosis. Its significance in cancer and cancer Therapy

Every cell in a multicellular organism has the potential to die by apoptosis, but tumour cells often have faulty apoptotic pathways. These defects not only increase tumour mass, but also render the tumour resistant to therapy. So, what are the molecular mechanisms of tumour resistance to apoptosis and how can we use this knowledge to resensitize tumour cells to cancer therapy?

/pdf/death-and-anti-death-tumour-resistance-to-apoptosis-4wqqeuiefw.pdf

Death and anti-death: tumour resistance to apoptosis

Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells.

Coregulation of the APO-1 antigen with intercellular adhesion molecule- 1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas

P.H. Krommert I. Behrmann,] V. Bier,2 P. Don/e/,1 J. Dhein,] M.H. FcrWc,3 G. Gcrrc/n,1 C . K/as,1 E. Knipping,] K.-M. Lücking-Famira,] S. Matzku* A. Oehm,] S. Richards,] B.C. Trauth,] G.W. Bornkamm,3 W. Falk,] P. Möller* and K.-M. Debatin2 institute for Immunology and Genetics, German Cancer Research Center, Heidelberg, Germany 2Children's Hospital, University of Heidelberg, Germany ^Institute for Clinical Molecular Biology/GSF, Munich, Germany ^Institute for Radiobiology and Pathophysiology, German Cancer Research Center, Heidelberg, Germany ^Institute for Pathology, University of Heidelberg, Germany

Apoptosis in the Apo-1 system

The APO-1 cellular membrane antigen, an about 50 kDa antigen associated with cellular apoptosis, and purified cDNA encoding same is described. The antigen is expressed by numerous normal and malignant cells, including activated and malignant lymphoid cells. Also disclosed are antibodies which bind the antigen, and which induce growth inhibition and apoptosis.

Monoclonal antibodies to the APO-1 antigen

Compsn. for inhibiting apoptosis comprises at least one of (1) an APO-1 inhibitor (I); (2) a cpd. (II) that inhibits or captures the APO-1 ligand and/or (3) a cpd. (III) that inhibits intracellular APO-1 signalling pathways, plus usual auxiliaries. (I)-(III) are recognised as foreign by the subject being treated. Also new are cpds. (IV) with at least one extracellular APO-1 domain plus a carrier, neither component being recognised as foreign.

Jens Dr Dhein

Papers

Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells.

Coregulation of the APO-1 antigen with intercellular adhesion molecule- 1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas

Apoptosis in the Apo-1 system

Monoclonal antibodies to the APO-1 antigen

APO-1 inhibitor compsn. inhibits apoptosis