title: Regulation of cellular processes by interleukin-16 in homeostasis and cancer.
abstract: Interleukin-16 (IL-16) is generated as a precursor molecule that is cleaved by caspase-3 to produce a pro-IL-16 molecule that functions as a regulator of T cell growth, and a secreted peptide that functions as a CD4 and/or CD9 ligand for induction of cell motility and activation. IL-16 has been predominantly studied as a contributing factor in the orchestration of an immune response; however, more recently IL-16 bioactivity has been closely associated with the progression of a number of different cancers. While the association between IL-16 plasma levels and tumor progression has been reported for many types of cancer, the mechanism for IL-16 involvement has been partially elucidated for three of the cancer types, cutaneous T cell lymphoma (CTCL), multiple myeloma (MM), and breast cancer. The mechanism for promoting cell growth is different in each of these cancers and involves a sequence mutation in the pro-molecule facilitating decreased p27(KIP1) levels in CTCL; over expression of the secreted IL-16 molecule to induce proliferation in CTCL T cells, and plasma cells in MM; and increased secreted IL-16 acting to recruit CD4+ pro-tumor macrophages in breast cancer. This article will review the cellular process for generating IL-16, the biological activities for both the pro- and secreted forms of the protein, and then the mechanism by which these forms contribute to cancer progression. As a soluble cytokine the ability to reduce or eliminate IL-16 synthesis through siRNA approaches or bioactivity through the use of neutralizing antibody treatment may represent a novel therapeutic approach.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jillian
authors.initials: J
authors.lastname: Richmond
authors.forename: Marina
authors.initials: M
authors.lastname: Tuzova
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
authors.forename: David
authors.initials: D
authors.lastname: Center
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019410:Interleukin-16