Cancer, the uncontrolled division of cells, is an evergrowing concern in the modern world and innovative solutions must be found constantly into combatting this
disease. One research team came up with a solution that may just revolutionise the future of oncology. Before we look at the study it is important to understand the nature of cancer and different factors that affect its spread- metastasis.
Firstly, Cellular plasticity-the ability of a cell to adapt to changes in its environment- has a critical role in the development of cancer cell survival, invasion, metastasis, and resistance. Cells can become dynamic and can be influenced by the environment through various cues, such as the presence of certain chemicals or the signalling pathways. An epithelial-mycetal transition (EMT) is a major contributor to the cell's ability to adapt to the environment. While EMT is responsible for the invasion of primary cancer cells, it is also involved in the development of metastatic outgrowth cells in distant organs. The role of EMT in this process is also evidenced by its reversal and its potential detrimental effects.
Non-transformed mammary epithelium cells have also been linked to increased cell surface area and the ability to generate multi-lineage differentiation. The observation that cancer cells de-differentiate is associated with an increased risk of developing cancer and the development of cancer-metastatic potential. The ability to induce cancer cell differentiation can be very successful in treating various types of malignancies. In humans, the introduction of all-trans Retinoic acid has been shown to induce the differentiation of acute promyelocytic leukaemia cells.
The research carried out hypothesised that cancer cell plasticity is essential for cancer cell dissemination and that it can be targeted and inhibited through a trans-differentiating approach. To test their theory, the research team used Py2T cells derived from mammary tumours of transgenic mice to study the effects of EMT on cancer cell plasticity. They also used mouse breast cancer cells derived from an omaveal tumour to develop an irreversible EMT model of the cell's fate. They carry alleles of the E-cadherin gene, which produce proteins called cadherins that act as adhesive bridges between cells, undergo an irreversible induction of their own E-cadherin ablation. (The loss of catherins is involved in the formation of epithelial type of cancers.)
Methods were used to investigate if breast cancer cells derived from the EMT can be induced to adipogenic. They were compared with 3T3-L1, a cellular adipogenesis model. The researchers optimized an adipogenesis protocol using 3T3L1 pre-Adipocytes, which are known to develop into adipocytes when stimulated with insulin, dexamethase, and Rosiglitazone. This protocol was also used to induce the growth of mammary gland tumours. The generation of adipocytes was readily detected in treated breast cancer cells but not in the treated epithelial counterparts. The expression of c/EBP was also present in the treated cells but not in the treated epithelial counterparts. The expression of c/EBP was not detected in the treated cells and could not be detected in the untreated cells. It was also not found in the treated cells of the mesenchymal lineage.
Two conclusions we stated by Professor Gerhard Christofori, senior researcher for the project:
"Firstly, we demonstrate that breast cancer cells that undergo an EMT and thus become malignant, metastatic and therapy-resistant, exhibit a high degree of stemness, also referred to as plasticity. It is thus possible to convert these malignant cells into other cell types, as shown here by conversion to adipocytes."
"Secondly, the conversion of malignant breast cancer cells into adipocytes not only changes their differentiation status but also represses their invasive properties and thus metastasis formation and their proliferation. Note that adipocytes do not proliferate anymore, they are called 'post-mitotic, hence the therapeutic effect."
In essence, this research shows great possibilities for being developed as an effective means of treating cancer. The full article can be found in the link below.
Article:
Ronen et al. Gain Fat--Lose Metastasis: Converting Invasive Breast
Cancer Cells into Adipocytes Inhibits Cancer Metastasis. Cancer Cell. (2019). Available at: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30573-7
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