Humans are jam packed with different cell types. Throughout your body you'll find epithelial cells, mesenchymal cells, nerve cells, endothelial cells, and a bewildering diversity of immune cells.
This complexity begs the question: why does biology bother? Can't we just have one cell type? What's the value in having so many different cells?
First, let's consider what makes each cell type different. For the most part, it's not DNA. The genome in your epithelial cells is largely identical to that in your fibroblasts. In contrast, the proteins expressed between different cell types are discrete. For example, epithelial cells express cell-cell adhesion proteins (enabling them to form an epithelium), whereas fibroblasts secrete extracellular matrix proteins (enabling them to organise tissue structure). Cell-specific proteomes enable cells to achieve specialised functions.
Signalling Societies
One consequence of cell-specific protein expression is that each cell type contains distinct signalling proteins. This enables each cell type to process signals completely differently. For example, the same protein cue can tell one cell type to grow, yet tell another cell to die. This cell-specific processing is called 'homocellular signalling'.
Although homocellular signalling is what most cell biologists study, it's a simplified view. In reality, all cells sit alongside other cell types in tissues.
When multiple cell types are combined, they can communicate with one another. This is called 'heterocellular signalling'.
Heterocellular signalling enables specialised cells to exchange information and expand their collective signal processing capacity. When viewed from this heterocellular perspective, tissues resemble diverse cellular societies — and despite right-wing rhetoric, societies benefit from diversity.
Specialisation and Exchange
In socioeconomic theory, there is a basic concept called 'specialisation and exchange'. The idea states that it's more productive for workers in a society to specialise in skills and then exchange these services — than to try and do everything yourself. For example, it would be extremely inefficient for everyone in a society to train to be a doctor, a computer programmer, and an actor. We'd end up with worse doctors, worse programmers, and Hollyoaks as the pinnacle of thespian achievement. Instead, some people specialise in medicine, some become expert programmers, and others go to acting school. When the doctor needs some software, they'll buy it from the programmer. When the programmer gets ill, they'll visit the doctor. When the doctor has time off (should such a thing happen), they can watch Daniel Day-Lewis.
By specialising and then exchanging skills, all parties get a better service and the whole society is more productive.
'Specialisation and exchange' is also found throughout biology. In tissues, homocellular signalling allows cells to specialise. Heterocellular signalling then allows cells to exchange information. This enables cells to combine forces to achieve phenotypes that no cell type can accomplish in isolation.
For example, consider something you use every day: your gut. Intestinal epithelial cells have specialised homocellular signalling that allow them to form an epithelium. This creates a barrier between the food you ate last night and your blood. However, if epithelial cells are combined with myeloid cells (antigen recognition) and lymphoid cells (antigen attacking), they can form a tissue epithelium with adaptive immunosurveillance. The diversity of multiple cell types creates a smart barrier that can simultaneously detect and kill pathogens. Such a complex phenotype can only be achieved when diverse cells work together — no one cell type can do it all.
Such collaborative behaviour is common in biology. Adaptive immunity, sight, digestion, and homeostasis are all complex phenotypes that require multiple cell types. In fact, pretty much every tissue phenotype can be said to 'supervene' upon heterocellular signalling.
Despite its ubiquity, the process by which multiple cell types collaborate to achieve complex phenotypes doesn't actually have a formal name. Biologists frequently discuss the products of such processes, but there is no turn-of-phrase to capture cellular specialisation and exchange.
In the absence of such language, I've taken the liberty of creating a term. I call it 'heterocellular emergence'.
Here's the 'dictionary' definition:
Heterocellular Emergence | ˌhɛt(ə)rəʊˈsɛljʊlə ɪˈməːdʒ(ə)ns | noun
- a process whereby complex tissue-level phenotypes are achieved through interactions between different cell types.
The Heterocellular Emergence of Cancer
Heterocellular emergence is found throughout metazoan life — and like many processes in healthy tissues, heterocellular emergence is also seen in cancer.
Just like healthy intestinal tissue, colorectal cancer (CRC) tumours also contain epithelial, mesenchymal, lymphoid, and myeloid cells. And, like healthy tissues, CRC tumours use these different cells to achieve complex phenotypes. The difference with cancer is that these phenotypes (such as immune evasion and metastasis) can kill, rather than aid, the host organism.
In a new article for Trends in Cancer entitled 'The Heterocellular Emergence of Colorectal Cancer' I argue that cancer is an emergent heterocellular phenotype.
It's half review, half an attempt to unify anecdotal tumour microenvironment observations into an emergent theory of malignancy. If you're interested in how different cell types collaborate in cancer, check it out.
