Growth factor autocrine

IL-2 acts as a critical autocrine growth factor for T-cells, and the magnitude of the T-cell response is largely dependent upon the level of IL-2 produced. IL-2 also serves as a growth factor for activated B-lymphocytes. In addition to promoting proliferation of these cells, IL-2 (as well as some other interleukins) stimulates enhanced antibody production and secretion. In this way, it effectively potentates the humoral immune response. 

Sabharwal, P. et al., Prolactin synthesized and secreted by human peripheral blood mononuclear cells An autocrine growth factor for lymphoproliferation, Proc. Nat. Acad. Sci., 89, 7713, 1992. 

As bombesin family peptides are thought to be autocrine growth factors for SCLC, the results described above suggested that kuwanon H... 

Kamohara H, Takahashi M, Ishiko T, Ogawa M, Baba H. 2007. Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells Impact of CXCL-8 as an autocrine growth factor. Int J Oncol 31 627-632. 

Thornton, M. J., Hamada, K., Messenger, A. G., and Randall, V. A. (1998). Androgen-dependent beard dermal papilla cells secrete autocrine growth factor(s) in response to testosterone unlike scalp cells. J. Invest. Dermatol. Ill, 727-732. 

Fig. 4. Schematic model of the mechanisms of oestrogen control of cell proliferation. Three different mechanisms are illustrated. In (1) the interaction of oestrogen (E) with ER leads to increased transcription of genes whose products are directly involved in the control of cell replication. The mechanism illustrated in (2) postulates that oestrogens modulate the production of autocrine growth factors which in turn bind to growth factor receptors at the cell surface and mitogenesis occurs as a consequence of growth factor-activated metabolic pathways. The underlying hypothesis in (3) is that cells are under inhibitory (I) control by undefined molecules in the extracellular fluid and that oestrogens block the effects of these inhibitory molecules.

Uhrbom L, Hesselager G, Ostman A, Nister M, Westermark B, Dependence of autocrine growth factor stimulation in platelet-derived growth factor-B-induced mouse brain tumor cells, Int. J. Cancer, 85 398-406, 2000. 

Recently Moody et al.,22) discovered that the C-terminal partial sequence of bombesin and bombesin-like peptides (BLPs) can function as autocrine growth factors in human small-cell lung cancer (SCLC) cell lines. 

Thioredoxin was shown to reduce the two interchain disulfides of insulin very efficiently around neutral pH and in the presence of either thioredoxin reductase and NADPH or lipoamide, lipoamide dehydrogenase and NADH [277,278], This reduction may be important in hormone action since the reduction of insulin disulfides is a prerequisite of proteolytic degradation of insulin. Thioredoxin has also been identified as the endogenous activator of the rat glucocorticoid receptor to a steroid-binding state [279]. Finally, recent data suggest that thioredoxin is secreted by immunocompetent cells and then behaves as an autocrine growth factor [280]. 

Bombesin and related peptides such as gastrin-releasing peptide, neuromedin B and somatomedin are autocrine growth factors, anorexigenic and inducers of GI hormone (e.g. gastrin) release. Bombesin acts via Gaq to elevate cytosolic Ca2+. 

NEUT-R agonist (4- cAMP (0.5 nM), TcGMP(lnM) [anorexigenic, autocrine growth factor for small cell lung cancer cells (SCLC cells), CNS NT, duodenum relaxation, ileum uterine contraction, mast cell Histamine release,... 

BB3-R agonist [anorexigenic, SCLC cancer cell autocrine growth factor, induces GI hormone release]... 

Activation of protooncogenes, inhibition or mutation of tumor suppressor genes, and production of autocrine growth factors contribute to ceUular proliferation and malignant transformation. Molecular changes, such as P53 mutations and overexpression of epidermal growth factor receptor, also affect disease prognosis and response to therapy. 

Avis, I. L., Kovacs, T. O., Kasprzyk, P. G., Treston, A. M., Bartholomew, R., Walsh, J. H., Cuttitta F. and Mulshine, J. L. (1991). PreeUnical evaluation of an anti-autocrine growth factor monoclonal antibody for treatment of patients with smaU-cell lung cancer. J. Natl. Cancer Inst. 83, 1470-1476. 

Lang, R. A. and Burgess, A. W. (1990). Autocrine growth factors and tumorigenic transformation. Immunol. Today 11, 244—249. 

IL-9 is produced by some activated T cells (mainly by activated CD4 Th2 lymphocytes for which it represents an autocrine growth factor) and Hodgkin s lymphoma cells (Figure 22-17). ... 

CIO. Cozzolino, F., Rubartelli, A., Aldinucci, D., Sitia, R., Torcia, M., Shaw, A., and Di Guglielmo, R., Interleukin 1 as an autocrine growth factor for acute myeloid leukemia cells. Proc. Natl. Acad. Sci. U.SA. 86, 2369-2373 (1989). 

The way to create a serum-free culture is to adapt the cells to the serum-free medium. In our laboratory, we tried to adapt a human lymphoblastoid cell line, Namalwa, from a medium containing 10% serum to serum-free. We were able to adapt Namalwa cell to a ITPSG serum-free medium which contained insulin, transferrin, sodium pyruvate, selenious acid and galactose in RPMI-1640. In the case of cell adaptation for production of autocrine growth factor, we were able to grow the cell line in serum- and protein-free media as well as in K5 62-K1 (T1) which produces an autocrine growth factor, LGF-1 (leukemia derived growth factor-1). 

Schadendorf, D., Moller, A., et al. (1993). IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol 151(5) 2667-75. 

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