Novel way to uncover tumor microenvironment proteomics

Chemotherapy once indiscriminately targeted any rapidly dividing cell, but increasingly, treatments are being tailored to the unique protein environment of cancer cells. To develop these treatments, scientists need to accurately characterize the complex protein architecture of these malignancies using proteomics. Proteins offer unique advantages because they are the ultimate products of the genetic code, reflecting what occurs in the cell.

Illustration of a macrophage, a phagocytic immune cell, engulfing cancer cells in the tumor microenvironment.

The biggest barrier to proteomics has historically been cost and time. High-throughput methods are required to make the technology feasible. To address this challenge, Shiri Karagach, Tamar Geiger and a team of researchers at the Weizmann Institute of Science developed a novel technique for characterizing the protein environment of cancer cells using a technique that allows for the higher throughput necessary to make the method more effective. They published these results in Molecular & Cellular Proteomics.

The team injected colorectal cancer cells into the tail veins of mice to induce metastasis to the lungs. To test the technique, researchers harvested the lungs, separated them into individual cells and ran them through their new single-cell proteomic analysis method. The main innovation involved 1,536 individual wells containing cells and semi-automated reagent transfer, improving both speed and reproducibility.

As a proof of concept, they isolated macrophages from the mice’s tumors using known protein markers. They found 575 significant differences in protein levels between tumor and control macrophages. For example, tumor macrophages upregulated major histocompatibility complex class I proteins and increased production of cytokines, both crucial in adaptive immunity.

This work demonstrates that the novel technique allows faster, more robust analysis of cancer proteomes, paving the way for broader applications in tumor biology.