Colon cancer microenvironments preventing invasion and metastasis

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Published: 20 Nov 2012
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Dr Makoto Mark Taketo – Kyoto University Graduate School of Medicine, Japan

Dr Makoto Mark Taketo talks to ecancer at the IFOM-Kyoto University Joint Symposium about his talk on the microenvironment of colon cancer using mouse models.


Dr Taketo recently began identifying the proteases, MMP9 and MMP2, which can be inhibited; however, there is no compound yet which has had success in clinical trials.

Can you tell us about your research?

The most important point we have discovered is that people… we had a sort of common knowledge or an impression that the cancer metastasis takes place simply because cancer cells just spread there and then keep growing. It turns out that the cancer cannot metastasise and then expand in the metastatic colonisation unless the host tissue helps the growth of this. So what we are calling it is a microenvironment which is the host tissue supplying the so-called niche for the cancer to survive there and then expand. So these are the mechanisms that we are studying and then we found recently that the bone marrow derived cells in fact are recruited by the cancer cells and then these bone marrow derived cells, namely that’s the host derived cells, are helping the cancer to expand by secreting the proteases that dissolve the surrounding tissues.

Have you started to identify some of these proteases?

We know actually the proteases have been known that these are called metalloproteinases such as MMP9 and MMP2, however, if the MMP inhibitors are used systemically they cause very severe side effects such as joint pain, headache and muscle ache. So in fact more than ten compounds have been tried and they all failed in clinical trials. So that is why we are focussing on the mechanism that recruits the bone marrow derived cells to the invasion front. So we coined this strategy as cellular targeting therapy instead of the molecular targeting therapy which is a systemic inhibition of the protease. We’re trying to block the recruitment of the protease secreting cells accumulating around the tumour invasion front.

What brings you to Italy?

This is the special occasion between Kyoto University and IFOM to develop the collaboration or interaction. So we are having this first symposium here in Milan.