Abdi, S. | bioRxiv Science

bioRxiv2025

Collagen-Based Tumor Spheroid Model for Investigating Tumor-Macrophage Interactions through Extracellular Matrix Remodeling

Macrophages in the tumor microenvironment (TME) can constitute up to 50% of tumor mass and play a critical role in cancer cell proliferation, invasion, and metastasis. While their contribution to extracellular matrix (ECM) degradation through matrix metalloproteinases (MMPs) has been explored, the role of other macrophage-derived factors in ECM remodeling and their impacts beyond degradation remain poorly understood. Here, we describe the development of a 3D collagen-based tumor spheroid model to investigate the impact of peripheral blood mononuclear cell (PBMC)-derived macrophages on cancer cell-ECM and cancer cell-macrophage interactions within the TME. We observed that cancer cells stimulated PBMC-derived macrophages into an M2-like phenotype and that tumor spheroid conditioned macrophages (TSCMs) shifted cancer cell populations toward phenotypes with greater invasion distances and reduced circularity, indicative of increased malignancy. Such observations can be explained by macrophage-mediated ECM remodeling. Specifically, we demonstrate that TSCMs secreted a variety of soluble factors that are known to contribute to ECM remodeling, including ECM degradation and fiber realignment. These processes collectively create a tumor-favoring environment by loosening the collagen matrix and aligning fibers that serve as invasion tracks for migrating tumor cells that facilitate cancer cell migration and invasion. This model provides a robust platform to study the interactions between cellular and non-cellular components in the TME and to identify the molecular mechanisms underlying cancer progression. These insights may aid in the development of novel therapeutic strategies targeting macrophage-mediated processes in cancer. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/679587v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@17d1f9forg.highwire.dtl.DTLVardef@1a71500org.highwire.dtl.DTLVardef@53deeeorg.highwire.dtl.DTLVardef@510268_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Modeling vehicle collision risk for the jungle cat in the Hyrcanian forests of Iran: A guide for vehicle collision prevention

Wildlife-vehicle collisions are an important wildlife conservation challenge, especially for carnivores. As in other countries, vehicle collisions pose a major threat to carnivores in Iran. The jungle cat (Felis chaus) is a small carnivore species facing multiple threats, including habitat destruction, land use changes, and particularly vehicle collisions. We collected data on jungle cat collisions to model jungle cat-vehicle collision risk in the Hyrcanian forests of northern Iran. We also modeled the jungle cat vehicle collision risk in the study area but by creating 1 km and 5 km buffers around the roads and identified high vehicle collision risk areas within the 1 km and 5 km butters. We used the Maxent model to identify most important predictors of collision risk. Our models showed that areas in west of Golestan province, east of Mazandaran province, and in central parts of Gilan province faced highest vehicle collision risk for the jungle cat in the Hyrcanian forests. Human footprint and slope were the most important predictors of the jungle cat vehicle collision, with 48.3% and 17.2% contribution and with positive and negative correlation respectively. Results of variable importance were similar when modeling area was limited to a 5 km buffer zone around the roads. But when modeling area was limited to a 1 km buffer zone around the roads, slope became insignificant. Collisions more likely occur where vegetation grows immediately adjacent to roads, so clearing a roadside strip would reduce potential collisions. We recommend that high collision-risk areas we identified for jungle cat in the Hyrcanian forests be a focus for future monitoring and conservation planning.

ecology↗