Redifferentiating brain tumour stem cells: the concept of cancer regenerative medicine

The trendy cancer stem cell theory highlights that there is a functional hierarchy between different tumour cells and only a small portion, the so called cancer stem cells have crucial role in initiating tumour growth. This assumption was confirmed in the case of blood, breast and brain for example. Based on that a new therapeutic approach of cancer is delineated which can induce differentiation of tumour cells rather then killing them. Indeed a very natural survivalProband useful stem cell targeted therapy by concept: redifferentiate cancer stem cells into harmless and in some cases useful functional tissue cells. I call it the concept of cancer regenerative medicine: redifferentiate all the tumour initiating cancer stem cells in a patient into functional tissue and organ cells. In Nature, 7 December Issue Piccirillo et al. addressed the question whether the stem-like tumour initiating cell subpopulation of a glioblastoma, marked with a specific antigen, CD 133+ can be differentiated with Bone Morphogenetic Protein (BMP) into a functional type of brain cells? Ok, vocabulary first: glioblastoma (GBM) is the most common adult malignant brain tumour, CD133+ is a neural precursor cell marker and the members of the BMP family make neural precursor cells differentiatie into mature astrocytes, glial cells. So the lab guys were dissociating solid tumour samples into single-cell suspensions and were testing their response to BMP. The large picture is that BMP treatment (specially BMP4) reduced cancer cell proliferation, induced astrocyte-like differentiation, effectively blocks the tumour growth and prolonges survival. During the in vitro line of the experiments treatment of fluorescence sorted CD133+ population with BMP4 caused greater then 70% reduction in the clonogenic index, the percentage of clone- forming neural precursors in GBM cells in vitro, decreased the size of the CD133+ pool and increased astroglial marker GFAP expression (GFAP immunoreactivity), while there was a reduced increase in neuronal (βIII tubulin and MAP5) and oligodendroglial GalC galactocerobroside ) antigens, which marks aberrant co-expression of neuronal and glial antigens unluckily. In vivo beads soaked with BMP delivered to the same intrastriatal place of immunodeficient mice as glioblastoma cells effectively reduced tumour size, prolonged survival (see graph, green, compared to GBM cell transplanted control animals, red). BMP4 treated cells do not form invasive tumours but small delimited lesions confined to the injection site with low mitotic index and no ventricular (3-4) migration. CD133+ cells could not be recovered from the small tumours, nor were capable of serial engraftment after. BMP-4 has a strong effect on receptor activation and triggering the Smad signalling cascade.
“These findings show that the BMP–BMPR signalling system—which controls the activity of normal brain stem cells—may also act as a key inhibitory regulator of tumour-initiating, stem-like cells from GBMs and the results also identify BMP4 as a novel, non-cytotoxic therapeutic effector, which may be used to prevent growth and recurrence of GBMs in humans.”
Problem could be that certain cancer cells survived the BMP-treatment which can lead to recurrence at a longer latency. This problem could be solved with improved purification of the subpopulation of CD133+ cells, so true cancer stem cells are expected at the exit!

Combined with classical therapy BMP rediff treatment can reduce the lethality of cancer patients.