QIMA Life Sciences has initiated a tissue engineering R&D program in order to develop a skin equivalent model incorporating melanoma cells.
After different tests on monolayer cultures, two cancer lines issued from melanomas (among those available in QIMA Life Sciences) were selected to be integrated as standard in a normal skin equivalent model (3D culture):
- A-375 line (ATCC® CRL1619): cells issued from metastatic melanoma
- WM266-4 line (ATCC® CRL1676): cells issued from metastatic melanoma
3D cell culture has allowed us to obtain 2 models corresponding to different stages of development and severity, in which:
- The A-375 line presents an aggressive profile and results in very important epidermis destruction and equivalent dermis invasion over culture time
- The WM266-4 line develops a less aggressive response: after 10 to 12 days of culture, the epidermis part of reconstructed skin shows fairly good histology and cancer cells form clusters that are easily identifiable in histology. The cluster size increases over culture time.
Figure 1: Immunohistofluorescence labeling of Pmel-17, Ki67 and S100 proteins in a reconstructed skin model with melanocytes and in reconstructed skin models with melanoma
Prospects
Our objective is to propose customized and coherent models and methods to respond to the issues faced by research or industry projects related to the melanoma. We can now offer the opportunity to use different models directly, either for pharmacological studies or to carry out partnership R&D programs related to melanoma research.
We currently have analytical solutions in cellular and molecular pharmacology in order to complete projects rapidly, but also to ensure the development of other methods of analysis. We benefit from a long-standing expertise in the development of protocols for the modeling of pathologies (inflammation, infection, senescence, degeneration) or aggression (UV stress, scarring).
Melanoma in a few words
Melanoma is a skin tumor linked to an uncontrolled proliferation of melanocytes. Although it accounts for only 3 to 5 cases in a population of 100,000, it represents 75% of causes of cancer mortality due to its extremely fast evolution and propagation. This phenomenon generally occurs following physical or chemical damage to the skin, such as damage caused by intense sun exposure. In most cases, a melanoma is discovered when a dark colored spot appears on the skin (80 per cent of cases) or when a pre-existing mole changes color or shape.
Figure 2: Reconstructed skin model with melanoma
Melanomas evolve in three different stages:
- First stage: radial growth phase (RGP): melanocytes multiply horizontally in an abnormal way and remain along the basal lamina
- Second stage: vertical growth phase (VGP): cells proliferate more quickly. They are able to multiply vertically and thus to invade dermis by a significant release of metalloproteinases. These proteolytic enzymes can degrade the extracellular matrix and the basal membrane and thus promote melanoma growth.
- Third stage: metastatic stage: the final growth stage of the melanoma when it acquires the capacity of intravasation and so can form metastases and spread to other organs
The mechanisms of transition between these different stages are not well understood as yet. However, several studies have made it possible to identify the genes implicated in these transitions.
