Under the sea: Recent VIB research on aquatic organisms leads to cancer insights
Sometimes, scientific discoveries in disease processes come from unlikely organisms, such as cockles or diseased flatfish
November 16, 2023
Every living organism, from the tiniest plankton to the largest whale, contributes a unique chapter to the story of our planet. With each discovery, we gain fresh insights, new perspectives, and sometimes groundbreaking revelations in the life sciences. In the ever-evolving world of science, breakthroughs come in all shapes and sizes, from transmissible cancers in cockles to potential anti-cancer agents discovered in flatfish bacteria.
Cancer in the waves
In humans, cancer is not contagious. And yet, in the animal kingdom, some cancers have found a way to spread from individual to individual. Devil facial tumor disease in Tasmanian devils is a famous example, as is canine transmissible venereal tumor, a sexually transmissible cancer in dogs.
But in the sea, we can also find contagious cancers, such as bivalve transmissible neoplasia (BTN), which affect cockles, a type of shellfish found along the coasts of Europe and northwest Africa. BTN is a cancer of the cockle’s immune cells, causing a leukemia-like condition that spreads throughout the body and is often fatal to its host.
A large international collaboration, which included Jonas Demeulemeester from the VIB-KU Leuven Center for Cancer Biology, created the first high-quality reference genome for the common cockle (Cerastoderma edule), which was crucial for tracing the evolution of contagious cockle cancers. The team gathered cockles from 36 locations across 11 countries and sequenced 61 BTN samples, revealing they represented two distinct cancers. Some cockles were even co-infected by cells from both cancer lineages simultaneously.
The biggest surprise, however, was the high degree of genetic instability the team observed in BTN, even after hundreds or thousands of years of evolution. The number and size of the chromosomes present in the cancer cells varied widely among different samples and even within cells from the same sample; a level of chromosomal instability far beyond what has been observed in human tumors. The cancer had also captured mitochondria, which are the cells' powerhouses, from their host cockles at least seven times in the past.
Understanding the genomic instability in these cancers has important implications for cancer research in general. While human cancer cells typically cannot survive high levels of chromosomal instability, these BTN cells have thrived in such conditions. This finding may provide valuable insights into future strategies for targeting human cancer cells. Still, the research is also critical for protecting cockle populations, as a food source and cornerstone species in many marine ecosystems.
Anti-cancer compounds in a diseased fish
It all started in 2006 when a mysterious disease swept through a Spanish population of cultured wedge soles – a flatfish species popular for human consumption. To pinpoint the responsible pathogen, researchers performed detailed genetic analyses, and they identified a new species of bacteria – Pseudomonas baetica – in the liver of one of these diseased flatfish.
Fast forward to today, a team of researchers led by Joleen Masschelein at the VIB-KU Leuven Center for Microbiology revealed that some genes of P. baetica are responsible for producing a group of anti-cancer agents known as oximidines. These oximidines are crucial in inhibiting mammalian V-ATPases, proton pumps linked to various human diseases, including cancer.
But that’s not all – the team has discovered not one, not two, but three novel oximidine variants with potent anti-cancer properties.
By harnessing the power of bioengineering, the researchers could alter Pseudomonas baetica's unique pathways that make these oximidines in a molecular ‘assembly line.’ As a result, the bacteria produced a structurally simpler yet equally effective oximidine that opens up new avenues for novel anti-cancer analogs.
From cockles to fish liver, scientific breakthroughs can hide in unlikely places...
Publications:
Bruzos, Santamarina, Garcia-Souto, et al. Somatic evolution of marine transmissible leukaemias in the common cockle, Cerastoderma edule. Nature Cancer, 2023.
Vriens, De Ruysscher, et al. Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents. Angewandte Chemie, 2023.
