Capture of circulating metastatic cancer cell clusters from lung cancer patients can reveal unique genomic profiles and potential anti-metastatic molecular targets - A proof-of-concept study

Sep 21, 2026

Uploaded by Liam

Metastasis remains the leading cause of cancer deaths worldwide, and lung cancer is among the most lethal malignancies. While lung cancer metastases can spread selectively to multiple organs, the genetic and molecular drivers of this process remain poorly defined. Research highlights metastatic cancer cell clusters (MCCCs) as key drivers, yet accessing these primary sources has been difficult. This study presents a proof-of-concept platform to capture MCCCs directly from patients’ whole blood using biomimicry-based margination and CD44 immunoaffinity, achieving >90% capture efficiency in model cluster spikes, and enabling differential morphology and genomic profiling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Introduction

Significance of metastatic cancer cell clusters

Non-small cell lung cancer and metastatic mechanisms

Challenges in isolating circulating metastatic cells

PLOS ONE OPEN ACCESS Citation: Kouhmareh K, Martin E, Finlay D, Bhadada A, Hernandez-Vargas H, Downey F, et al.(2024) Capture of circulating metastatic cancer cell clusters from lung cancer patients can reveal unique genomic profiles and potential anti-metastatic molecular targets: A proof-of-concept study. PLoS ONE 19(7): e0306450 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0306450 Editor: Dominique Heymann, Universite de Nantes, FRANCE Received: February 28, 2024 Accepted: June 18, 2024 Published: July 31, 2024 Copyright: © 2024 Kouhmareh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: 1. SBIR Grant from the National Cancer Institute 1R43CA261362-01 a. [https://reporter.nih](https://reporter.nih). gov/project-details/10255872 2. CCSG Grant P30CA23100 supporting the Biorepository and Tissue Technology Shared Resource at UCSD RESEARCH ARTICLE Capture of circulating metastatic cancer cell clusters from lung cancer patients can reveal unique genomic profiles and potential anti-metastatic molecular targets: A proof-of-concept study Kourosh Kouhmareh1¤a, Erika Martin1, Darren Finlay2, Anukriti Bhadada3¤b, Hector Hernandez-Vargas4, Francisco Downey3¤c, Jeffrey K. Allen3, Peter Teriete3,5 * 1 PhenoVista Biosciences, San Diego, CA, United States of America, 2 National Cancer Institute Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States of America, 3 TumorGen Inc. , San Diego, CA, United States of America, 4 Centre L´eon B´erard, Lyon, France, 5 IDEAYA Biosciences, South San Francisco, CA, United States of America ¤a Current address: Pathology Department, University of California San Diego, La Jolla, CA, United States of America ¤b Current address: NanoCellect Biomedical, Inc. , San Diego, CA, United States of America ¤c Current address: Department of Bioengineering, University of California San Diego, La Jolla, CA, United States of America * [pteriete@tumorgen.net](pteriete@tumorgen.net) Abstract Metastasis remains the leading cause of cancer deaths worldwide and lung cancer, known for its highly metastatic progression, remains among the most lethal of malignancies. Lung cancer metastasis can selectively spread to multiple different organs, however the genetic and molecular drivers for this process are still poorly understood. Understanding the heterogeneous genomic profile of lung cancer metastases is considered key in identifying therapeutic targets that prevent its spread. Research has identified the key source for metastasis being clusters of cells rather than individual cancer cells. These clusters, known as metastatic cancer cell clusters (MCCCs) have been shown to be 100-fold more tumorigenic than individual cancer cells. Unfortunately, access to these primary drivers of metastases remains difficult and has limited our understanding of their molecular and genomic profiles. Strong evidence in the literature suggests that differentially regulated biological pathways in MCCCs can provide new therapeutic drug targets to help combat cancer metastases. In order to expand research into MCCCs and their role in metastasis, we demonstrate a novel, proof of principle technology, to capture MCCCs directly from patients’ whole blood. Our platform can be readily tuned for different solid tumor types by combining a biomimicrybased margination effect coupled with immunoaffinity to isolate MCCCs. Adopting a selective capture approach based on overexpressed CD44 in MCCCs provides a methodology that preferentially isolates them from whole blood. Furthermore, we demonstrate a high capture efficiency of more than 90% w

FAQs

Why are metastatic cancer cell clusters important in lung cancer metastasis?

The study explains that MCCCs are strongly associated with metastatic spread and have been shown to be far more tumorigenic than individual cancer cells. Access to these clusters is critical for understanding the molecular drivers of metastasis.

How does the proposed platform capture circulating MCCCs from patient whole blood?

It uses a biomimicry-based margination effect combined with immunoaffinity to isolate MCCCs. A selective capture approach based on overexpressed CD44 preferentially enriches MCCCs from whole blood.

What performance and analysis results does the study report for captured MCCCs?

The platform demonstrates high capture efficiency, exceeding 90% when model MCCC-like clusters are spiked into whole blood. Captured MCCCs show highly differential morphologies and genomic profiles based on immunofluorescence staining and genomic analyses.

Sep 21, 2026

Uploaded by Liam