Our research focuses on the interaction of cancer cells with the host vasculature and the circulating blood cells. The interactions between tumour cells and the host vasculature are important in the initiation of metastases (secondary cancer) as well as allowing metastatic colony growth later in metastatic progression. Our work has indicated the importance of coagulation and platelets in recruiting myeloid cells to allow the earliest formation of metastatic colonies. Later in metastasis, recruitment of myeloid cells is also essential for colony growth and the formation of blood vessels in the colonies. We are asking how these myeloid cells enable metastatic progression. This work is beginning to identify targets both for detection and for treatment of metastatic lesions.
Figure 1: Tumour cell (green) metastatic to the lung endothelium (red) surrounded by platelets (blue).
Tumour vascularity is essential for the response of cancers to radiation therapy. During therapy, hypoxia (low oxygen) is highly detrimental to effective radiation therapy. Hypoxia is of course determined by tumour vascularity and oxygen consumption. We have begun to develop strategies to reduce hypoxia during radiation by identifying agents that lead to better blood vessel formation, also called vascular normalisation, and strategies to reduce tumoural oxygen consumption. These strategies would be expected to generate tumours that are less hypoxic and more responsive to radiation therapy. Clinical trials are underway based on this work.
The final outcome of radiation therapy is also affected by tumour regrowth at the end of therapy. We have shown that inhibition of vascular regrowth leads to enhanced efficacy of radiation therapy. We are currently exploring the mechanisms that tumours treated with radiation use to stimulate vascular growth and the means to interfere with this growth.
Figure 2: Tumour cell (blue) clot (red) formation, triggered by expression of Tissue Factor, promotes the recruitment of a population of monocytes/macrophages (green) that enhance tumour cell survival. This is a phenomenon that occurs at the very early stages of metastasis and it is also observed during the formation of premetastatic niches.