VASGBI Project Grant
Effects of opioids on angiogenesis
Professor Dave Lambert
Background
In the UK more than 331,000 people were diagnosed with cancer in 2011; equating to a diagnosis every 2mins. Half of all patients diagnosed will survive for at least 5 years. One of the major treatments for cancer is surgical removal and this requires some form of anaesthesia. There is now growing evidence that opioid drugs used for pain relief during anaesthesia worsen outcomes from cancer surgery. In terms of tumour survival, increased growth/migration, reduced patient immunity and increased growth of blood vessels (angiogenesis) supplying the tumour are all predicted to be 'tumour beneficial'. Opioids interact with opioid receptors of which there are four subtypes. The receptor for morphine is the one that almost all clinical drugs target. Opioid receptors are found in tumours where they increase migration, opioids also depress immunity and stimulate angiogenesis. In essence perioperative opioid use in cancer surgery represents 'the perfect storm'.
Aims
(i) to examine, in the test tube, the effects of opioid receptor activation on tissues that make up blood vessels and (ii) to examine the effects of opioid treatment on angiogenesis in a strain of mice prone to develop aneurysms. Our hypothesis is that opioids will increase angiogenesis and there will be differences among the four opioid receptor subtypes. A further specific aim is to allow the PI, Professor Lambert to translate opioid expertise into the cardiovascular area and pump prime a larger application to BHF.
Methodology
In the test tube we will assess opioid receptors present in different tissues by measuring the genetic message that produces them. We will measure function of these receptors (including angiogenesis) using standard techniques that we have used in the past including assays of cell survival, growth and migration. What is particularly novel is the use of opioids in a mouse model of aneurysm formation in which there is substantial angiogenesis. We will treat these mice with drugs that activate the four opioid receptor subtypes and then examine angiogenesis and outcome.
Expected Outcomes
This is primarily a pump priming application for a larger BHF grant submission. If there are differences in angiogenesis for opioid receptor subtypes then this will strengthen the logic for generation of analgesics that target beyond the morphine receptor or opioid blockers that do not get into the brain (reversing the peripheral effects at the tumour but not blocking pain relief).
Implications
This is clearly very early stage exploratory work but we believe it is the first of its kind to systematically examine the whole opioid family. Professor Lambert has been working for several years in the design of opioid drugs that target more than one subtype of receptor; these may offer substantial advantages over morphine in cancer surgery and for patients living with cancer (and pain).
Please see the NIAA's position statement on the use of animals in medical research.
