Cancer Enigma: Can We Outsmart Metastasis Before It Takes Flight?

Have you heard of the Great Banyan?

It is claimed to be the world's largest banyan tree.

"Estimated to be more than 250 years old, the Great Banyan is a looming figure, towering over everything else at Acharya Jagadish Chandra Bose Indian Botanic Garden in Shibpur, Howrah, Kolkata, West Bengal, India. The tree alone occupies an area of 4.67 acres!"(Times of India)

Can you appreciate a resemblance to the secret behind the immortal life of cancer cells with the Great Banyan?

Picture this: If cancer is the Great Banyan, metastases are the crafty branches. The go-to strategy to treat cancer so far has been wielding the surgical axe to chop off the trunk, thinking we've got it all figured out.

Reports say that The Great Banyan lost its original trunk to disease in 1925. But it didn’t stop the tree from growing. It grew bigger with "a total of 3772 aerial roots to be precise".

Today the entire botanical garden is actually one single tree!

It is kind of a similar situation to treating cancer. Isn't it?

Why do those sneaky cancer cells keep coming back, spreading havoc in different corners of the body and leaving medical experts puzzled and intrigued?

We probably do not have an absolute answer yet.

In the past, there was a belief that only large tumours could go rogue and become metastatic because of their huge size and a lot of acquired genetic mutations.

However, recent research data spills the beans! Even tiny tumours, housing fewer than 1000 cells, can send out cells into the bloodstream. This is NOT a good news.

And guess what? By the time most tumours are diagnosed, it's like a covert operation already happened.

What goes wrong?

During its journey from a normal cell to a cancerous one, internally the cell attracts a lot of genetic changes (genotype). The external appearance of the cancer cell (phenotype) also undergoes a drastic change.

For a long time, the big debate that existed in the cancer community was......

.....what causes metastasis?

Some scientists believed that the ability of an epithelial cell to be converted into a mesenchymal cell [called epithelial-to-mesenchymal transition (EMT) ] was the secret handshake to metastasis, while others argued that just having mesenchymal cells wasn't enough.

What is EMT?

"Epithelial-mesenchymal transition (EMT) is a crucial cellular program that enables polarized epithelial cells to transition toward a mesenchymal phenotype with increased cellular motility.

EMT plays essential functions during embryonic development. On the other hand, EMT is also aberrantly activated under pathological conditions including organ fibrosis and cancer." (doi: 10.1016/j.devcel.2019.04.010)

Cancer cells use EMT to facilitate their dissociation from the primary tumour. In this way, they acquire the metastatic phenotype to disseminate into blood circulation.

EM Plasticity (EMP) & Metastasis

A game-changer concept - EM Plasticity (EMP)- was introduced in the world of cancer biology in recent times.

It is the ability of cells to maintain their plasticity and transit between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states.

These cell transitions allow them to migrate from the primary tumour and invade the secondary site.

EMP seems like the aerial roots of the Great Banyan which keep it growing even in the absence of the main trunk!

EMP is associated with migration, invasion, colonisation, self-renewal and drug resistance of cancer cells.

But here comes the million-dollar question.....

What is the threshold of required EMT or MET to initiate the process of metastasis? It's a puzzle, my friends, and it doesn't play by the same rules for every type of cancer.

Food for thought:

One thing is clear with this sneak peek into the groundbreaking efforts to demystify metastasis.............it's not just about cutting off the branches anymore!

It's about understanding the intricate dance of cancer cells and staying one step ahead. Who knows, maybe one day we'll have a playbook to outsmart metastasis before it even thinks about spreading its wings!

Stay tuned, because in the world of science, every discovery brings us closer to cracking the code of this relentless foe.

Can we imagine that one day we might have a personalised scorecard for each cancer patient predicting their probability of metastasis?