Publication

Activin Signalling in Human Melanoma Cells

Susanna Eveliina Kallioinen
2012
Theses

Abstract

Melanoma, the most fatal of all skin cancers, by unknown mechanisms overcomes the cytostatic effects of TGFβ, while maintaining the TGFβ signaling needed for its tumor promoting functions. Besides TGFβ, ectopic induction of the TGFβ family member Nodal has been reported in human melanoma to correlate with progression to metastatic growth. The same authors reported that a Smad2 morpholino antisense oligonucleotide delays Nodal-induced tumor growth of the aggressive melanoma cell line C8161 in xenograft assays. To investigate the underlying molecular mechanism, we compared C8161 melanoma cells with isogenic poorly metastatic C81-61 cells reportedly lacking Nodal expression. Unexpectedly, reverse transcription PCR, Western blot analysis using specific antibodies, and activity assays revealed that metastatic C8161 cells and many other human melanoma cell lines and tumors do not express Nodal, but frequently upregulate the related ligand Activin A. However, siRNA knockdown of Activin A did not reduce invasiveness of C8161 cells in matrigel, nor did the overexpression of Activin A in C81-61 cells increase it. The activity of Smad2,3 signaling was evaluated in the melanoma cell lines by a seriesWestern blot and reporter assays. The Smad signaling pathway was found to be attenuated in both C8161 and C81-61 cell lines, as only a small fraction of total Smad2,3 was detected in the nuclear fraction of the melanoma cells. In addition, little Smad3 signaling activity was observed by a Smad3-dependent luciferase reporter. To evaluate paracrine effects, human melanoma cells that do or do not express exogenous Activin A or Nodal were xenografted into nude mice. Neither Activin A nor Nodal enhanced metastatic growth in this assay. Inhibition of Activin A did also not alter metastasis formation. However, in the presence of the human fragment crytallisable region (Fc), Activin A seems to enhanced metastatic growth. Further studies are required to confirm these results, and to find the mechanism by which Activin A enhances metastatic potential.

Official source

https://infoscience.epfl.ch/entities/publication/62ab353a-6900-4334-9c51-1bc459e5c10c

Susanna Eveliina Kallioinen
2012
Theses

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/62ab353a-6900-4334-9c51-1bc459e5c10c

Related concepts (29)

Melanoma

Melanoma, also redundantly known as malignant melanoma, is a type of cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown.

Paracrine signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling.

Skin cancer

Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death.

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