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Updated: Jul 6, 2026
A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model
Leanne C Huysentruyt1, Purna Mukherjee, Dia Banerjee
1Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Abstract:
Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs, and is the primary cause of morbidity and mortality for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of in vivo metastatic models that represent the full spectrum of metastatic disease. Here we identify 3 new spontaneously arising tumors in the inbred VM mouse strain, which has a relatively high incidence of CNS tumors. Two of the tumors (VM-M2 and VM-M3) reliably expressed all of the major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation and secondary tumor formation involving liver, kidney, spleen, lung and brain. Metastasis was assessed through visual organ inspection, histology, immunohistochemistry and bioluminescence imaging. The metastatic VM tumor cells also expressed multiple properties of macrophages including morphological appearance, surface adhesion, phagocytosis, total lipid composition (glycosphingolipids and phospholipids) and gene expression (CD11b, Iba1, F4/80, CD68, CD45 and CXCR4). The third tumor (VM-NM1) grew rapidly and expressed properties of neural stem/progenitor cells, but was neither invasive nor metastatic. Our data indicate that spontaneous brain tumors can arise from different cell types in VM mice and that metastatic cancer can represent a disease of macrophage-like cells similar to those described in several human metastatic cancers. The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management.
Insights
Researchers identified two new mouse brain tumor models (VM-M2 and VM-M3) that mimic cancer metastasis. These models exhibit macrophage-like properties and can aid in developing new cancer therapies.
Area of Science:
- Oncology
- Cancer Metastasis Research
- In Vivo Tumor Models
Background:
- Metastasis, the spread of cancer, is the leading cause of cancer-related death.
- Current therapies struggle to manage metastatic disease due to a lack of effective in vivo models.
- The VM mouse strain exhibits a high incidence of central nervous system (CNS) tumors.
Purpose of the Study:
- To identify and characterize novel, spontaneously arising metastatic tumor models in VM mice.
- To evaluate the metastatic potential and cellular properties of these new tumor models.
- To establish a valuable tool for studying cancer metastasis and therapeutic development.
Main Methods:
- Identification of three spontaneous tumors in inbred VM mice.
- Assessment of metastatic processes (invasion, intravasation, extravasation, secondary tumor formation) using histology, immunohistochemistry, and bioluminescence imaging.
- Characterization of metastatic VM tumor cell properties, including macrophage-like features and gene expression.
Main Results:
- Two tumors (VM-M2, VM-M3) demonstrated reliable metastatic capabilities to multiple organs (liver, kidney, spleen, lung, brain).
- Metastatic VM tumor cells exhibited macrophage characteristics in morphology, adhesion, phagocytosis, lipid composition, and gene expression (CD11b, Iba1, F4/80, CD68, CD45, CXCR4).
- A third tumor (VM-NM1) was non-invasive and non-metastatic, originating from neural stem/progenitor cells.
Conclusions:
- Spontaneous brain tumors in VM mice can originate from diverse cell types.
- Metastatic cancer may arise from macrophage-like cells, mirroring findings in human cancers.
- The VM-M2 and VM-M3 models offer a robust platform for investigating metastasis and testing anti-cancer therapies.
