Biochemical and functional study of post-translationally modified CXC chemokines in the tumor microenvironment

Solid tumors not only include tumor cells but also connective tissue cells, blood vessels and inflammatory cells (white blood cells or leukocytes), all of which are interposed between the malignant cells and normal host tissue. This stroma is required to reach tumor sizes beyond 2 mm, as it provides oxygen, nutrients and growth factors which promote proliferation, invasion and metastasis of the malignant cells. Thus, a detailed understanding of the tumor stroma itself and of its interactions with tumor cells will help in the development of new treatments for cancer patients. Chemokines, messenger proteins of the immune system, were originally discovered as signposts guiding leukocytes to places of injury. More recently it was found that many other cell types respond to chemokines and that chemokines after binding to their receptors not only trigger cell migration but also induce cell proliferation, survival and activation (gene transcription and protein secretion, e.g. of growth factors for the vasculature and tumor cells). Since chemokines are produced by tumor cells and virtually all stromal cell types, this spectrum of activities also affects the progression and growth of tumors. In this project we aim to enhance our understanding of the interplay between inflammatory cells, tumor cells and stromal cells and more specifically of how chemokines shape the tumor via their effects on the tumor stroma. Our findings may lead to the development of innovative cancer therapies.