Harnessing nanotechnology to understand tumor behavior

A new study led by pre-Ph.D. researcher Pablo S. Valera demonstrates the potential of surface-enhanced Raman spectroscopy (SERS) to explore metabolites secreted by cancer cells in cancer research.

The study, led by Ikerbasque research professors Luis Liz-Marzán (from CIC biomaGUNE) and Arkaitz Carracedo (from CIC bioGUNE) and to which other researchers from both centers, also members of the Networking Biomedical Research Center (CIBER ), participated. thus, provides valuable information to guide more specific experiments to reveal the function of these secreted metabolites in the tumor microenvironment or environment, which could lead to new therapeutic strategies.

The work is published in the journal Proceedings of the National Academy of Sciences.

The tumor microenvironment is a complex ecosystem formed by interactions between the tumor and healthy cells. It is a dynamic pseudo-organ that determines the development and progression of cancers. Although attention has traditionally focused on intercellular communication mediated by protein messengers, attention has recently turned to metabolites (or small compounds) secreted by tumors into the extracellular space.

Traditional techniques for tracking these metabolites in complex cellular contexts are limited, but surface-enhanced Raman spectroscopy (SERS) has emerged as a promising alternative due to its simplicity of operation.

In this study, a SERS-based strategy proposes to “investigate metabolites secreted by tumor cells lacking methylthioadenosine phosphorylase (a common genetic event associated with poor prognosis in various types of cancer, such as breast cancer and glioblastoma),” Valera explained. SERS “is a spectroscopic technique that uses gold nanoparticles to detect molecules in a biofluid. It is a fairly rapid technique, in which no sample pretreatment is required,” he added.

Cellular communication caused by metabolites secreted by tumor cells

Using SERS, researchers discovered that these cells secrete purine metabolites, which can be metabolized by healthy cells, giving rise to molecular changes consistent with the aggressiveness of the cancer; this explains the never before seen reprogramming of the tumor environment in cancers with suppression of methylthioadenosine phosphorylase.

“We were able to detect this metabolite, not only in the tumor cells but also in the rest of the healthy cells that are in contact with the tumor cells. We therefore detected that there is a relationship between the tumor cells and the healthy cells thanks to to this. metabolite, and that it also causes a change in the behavior of healthy cells, so that to some extent they help the tumor to grow,” Valera said.

It is worth emphasizing that “the complexity of these interactions in cancer patients could, in turn, pave the way for new therapeutic approaches,” he added.

The successful application of SERS in this study demonstrates that this technology could accelerate the ability to rapidly capture metabolic interactions in complex environments. Indeed, the simple and rapid acquisition of signals in SERS, as well as its high sensitivity, meet the requirements of being a front-line tool that can later guide more specific analyses.

A comprehensive picture of the metabolic state of the tumor microenvironment can be obtained by monitoring with complementary techniques. It is also important to highlight that effective synergy between SERS and other analytical methods has been demonstrated.