Scholarlink

Purpose <p>Cancer metastasis is the primary cause of cancer-related mortality, and this process is initiated by the invasion of tumor cells into surrounding tissues. Three-dimensional (3D) spheroid invasion assays are widely used to study tumor invasion in triple-negative breast cancer (TNBC), yet reported invasion patterns of MDA-MB-231 spheroids in basement membrane extract (BME) systems vary considerably. The physicochemical determinants underlying this variability remain poorly defined.</p> Methods <p>Here, we use time-lapse z-stack imaging combined with quantitative tracking of matrix-associated landmarks to investigate how pre-invasive cellular organization, matrix composition, and spatial heterogeneity influence invasion behavior in MDA-MB-231 multicellular tumor spheroids cultured in the presence and absence of Invasion Matrix (IM).</p> Results <p>Prior to invasion, peripheral cellular aggregates undergo morphological reorganization, while exploratory protrusions exhibit dynamic extension, retraction, merging, and bifurcation events that ultimately give rise to a reduced number of dominant protrusive branches. Matrix composition influences invasion-associated behavior, with reduced collagen density accelerating extracellular matrix (ECM) displacement and altering the spatial organization of spheroid-associated cells. In addition, distinct protrusion morphologies were observed at different focal planes within the same spheroid, highlighting spatial heterogeneity in invasion-associated phenotypes.</p> Conclusion <p>These findings demonstrate that invasion in spheroid models is preceded by dynamic cellular and matrix-associated processes and is influenced by matrix composition and spatial heterogeneity. Together, these observations provide a framework for understanding variability in spheroid invasion assays.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pre-invasive compaction and spatial organization influence invasion patterns in MDA-MB-231 spheroids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月6日

查看全文
  • You-shin Chen,
  • Dulce Ciuffetelli,
  • Meaghan Snider,
  • Yi-Chun Chen,
  • Katheren Barger,
  • Chloe Horcha-Fuwell,
  • Joseph Sucic

摘要

Purpose

Cancer metastasis is the primary cause of cancer-related mortality, and this process is initiated by the invasion of tumor cells into surrounding tissues. Three-dimensional (3D) spheroid invasion assays are widely used to study tumor invasion in triple-negative breast cancer (TNBC), yet reported invasion patterns of MDA-MB-231 spheroids in basement membrane extract (BME) systems vary considerably. The physicochemical determinants underlying this variability remain poorly defined.

Methods

Here, we use time-lapse z-stack imaging combined with quantitative tracking of matrix-associated landmarks to investigate how pre-invasive cellular organization, matrix composition, and spatial heterogeneity influence invasion behavior in MDA-MB-231 multicellular tumor spheroids cultured in the presence and absence of Invasion Matrix (IM).

Results

Prior to invasion, peripheral cellular aggregates undergo morphological reorganization, while exploratory protrusions exhibit dynamic extension, retraction, merging, and bifurcation events that ultimately give rise to a reduced number of dominant protrusive branches. Matrix composition influences invasion-associated behavior, with reduced collagen density accelerating extracellular matrix (ECM) displacement and altering the spatial organization of spheroid-associated cells. In addition, distinct protrusion morphologies were observed at different focal planes within the same spheroid, highlighting spatial heterogeneity in invasion-associated phenotypes.

Conclusion

These findings demonstrate that invasion in spheroid models is preceded by dynamic cellular and matrix-associated processes and is influenced by matrix composition and spatial heterogeneity. Together, these observations provide a framework for understanding variability in spheroid invasion assays.