Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.

bioRxiv : the preprint server for biology
Authors
Abstract

Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within cancer cells and extrinsic alterations in the microenvironment cooperate to drive different stages of tumor progression. Here, we integrate high-resolution spatial transcriptomics and evolving lineage tracing technologies to elucidate how tumor expansion, plasticity, and metastasis co-evolve with microenvironmental remodeling in a -driven mouse model of lung adenocarcinoma. We find that rapid tumor expansion contributes to a hypoxic, immunosuppressive, and fibrotic microenvironment that is associated with the emergence of pro-metastatic cancer cell states. Furthermore, metastases arise from spatially-confined subclones of primary tumors and remodel the distant metastatic niche into a fibrotic, collagen-rich microenvironment. Together, we present a comprehensive dataset integrating spatial assays and lineage tracing to elucidate how sequential changes in cancer cell state and microenvironmental structures cooperate to promote tumor progression.

Year of Publication
2024
Journal
bioRxiv : the preprint server for biology
Date Published
10/2024
ISSN
2692-8205
DOI
10.1101/2024.10.21.619529
PubMed ID
39484491
Links