In the series of posts Cancer On The Move I’ve been exploring how cancer cells start moving around away from the core of the tumor, enter the blood vessels and reach every corner of the body, eventually exiting the capillaries. Once this happens, cancer cells begin multiplying again, forming a secondary tumor or metastases. The process of forming secondary tumors is long and very intricate, as cancer cells need to carve a life for themselves in new and unfamiliar territory.
One of the most fascinating aspects of “setting up shop” for a cancer cell is to co-opt other cells and chemical signals that are innocently present in the tissue surrounding them. This collection of cells and signals is known as the “tumor micro-environment” or the “metastatic niche” and is the object of much of the most exciting cancer research being carried out right this second in hundreds on institutions worldwide. The most exciting example of what cancer cells can do to change their environment is the activity of breast cancer cells in the bone.
Our bones are an interesting mix of bone matrix, the hard stuff that makes our bones such a good support system, intertwined with blood vessels and other cells. In particular, two types of specialized cells are responsible for constantly re-modelling and molding the bone: osteoblasts and osteoclasts. Osteoclasts are continually chipping away at our bones, while osteoblasts are continually producing more bone substance. This allows for a continual renewal of the bone structure, forming a healthy and sturdy structure. Most importantly, when a bone breaks, osteoblasts make up new bone to mend the break. Once breast cancer cells land in the bone, they begin the process of undermining the bone structure by signalling to activate osteoclasts. This throws off the balance of bone being chewed up/bone being produced, which in turn leads to osteoclasts essentially carving up a new home for cancer cells to grow in.
The other interesting thing about this stage of cancer metastasis is that cancer cells need to switch back from an invasive to a proliferative mode. Let me explain. Cancer cells in the original tumor – for example in the breast cancer tumor in the breast – are multiplying at a terrifying speed. This means they have modified their genetic blueprint to drive cell division really rapidly, which is known as a proliferative mode. When they begin moving around, cancer cells stop multiplying quite so quickly and start moving around instead. This means they modify their genetic blueprint to enhance their ability to move, to the detriment of the ability of the cell to divide quickly. This is known as the invasive mode. However, when cancer cells get to their metastatic site they need to switch back to multiplying, which involves upsetting their genetic blueprint once again. Understanding this mechanism is especially interesting as it is a fantastic target for new drugs that might be able to stop cells from “switching back”. Cells that can’t switch back wouldn’t be able to form secondary tumors, and would eventually get mopped up by the natural immune system or by targeted chemotherapy.