Tumor Invasion and Metastasis: Overview

00:00 Okay, welcome back. In this next lecture, we're going to be talking about how tumors invade into the vasculature. That's not just blood vessels but could also be lymphatics.

00:12 And then how they successfully go some place else and start their own little colony in a far flung place otherwise known as metastasis. Alright, get ready, hold on to your seats.

00:25 So invasion metastasis is 3rd in our kind of roadmap of where we're going with the biology of neoplasia and we'll start here, we've actually seen this one before. You have a tumor that transforms into a malignant cell. It's got all the features of malignancy. But because of genetic instability, you acquire a whole bunch of other traits so that the final product that tumor clone at the very end is really, yes there are some driver mutations, but it is really a combination of multiple cell types and not all of them are going to be capable of metastasis.

01:05 In fact, the metastatic cell may have acquired other features, it really has acquired other features that allow at that particular trick. But in the primary tumor, the vast majority of the cells probably have not learned how to do this. We'll come back that because metastasis is actually a relatively rare thing. That's because the cells that are capable of doing that have to have learned multiple new tricks. It's a little bit like being at decathlete You can't just be someone who can do a shot put really well, you also have to run fast and you have to be able to jump high, you have to be doing multiple things if you're going to be a successful metastatic cell. So, tumor metastasis is a multistep process. You need to acquire multiple new abilities. Here we're looking at a tumor, the green cells, the lovely green cells are our tumor transform cells. They're in their original site. So, we've got them up there and they need to get across that basement membrane as indicated, crawl in between endothelial cells, and get out into the vasculature. So there has been some growth, some diversification, some angiogenesis. But to get out, the tumor has to crawl up between endothelial cells, break down the basement membrane and there is a metastatic subclone who has learned those tricks. It's now going to be in the circulation. Those tumor cells circulate and then at some point they have to stop, drop, adhere to the vessel wall, and crawl out at the other end. So there's going to be involvement of adhesion molecules and invasion. Again break down the basement membrane and some sort of chemotactic mechanism to draw them in to their new location. There are a lot of steps in there. And that's not just one thing that they have to learn. So a single cell in order to metastasize, a single cell must possess all the properties. It's going to be able to break down the basement membrane. It's got to separate from its other cells, break down the basement membrane, squeeze between endothelial cells, survive in the vasculature, stick some place else, breakdown the basement membrane again, and crawl out instead of shop some place else that may require angiogenesis. So, it may step along the way. If the cell has not learned how to do all of those things, it won't survive. So, that means that truly metastasis is a relatively rare event; however, if you have a gazillion cells in a tumor, odds are one of them will have learned all the tricks. So, important point to also remember as we're getting very clever with our technology, we can actually see circulating tumor cells. We can pull them out of the vasculature and enumerate them and see what properties they have. And if we do the experiment in mice, we already know that millions of tumor cells probably circulate everyday, released into the circulation. But in most of those mouse models, it's a rare event that a metastasis will actually take hold some place else. The circulating tumor cells also therefore don't necessarily mean that there's going to be metastatic doom. Simply finding cells in the circulation does not equal metastasis. It's a necessary predicate, you can have metastasis unless the cell circulate, but just having them there in the circulation doesn't mean "Oh my God the patients may have metastatic disease stage 4."