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Updated: Jul 16, 2026

A Label-Free Segmentation Approach for Intravital Imaging of Mammary Tumor Microenvironment
Published on: May 24, 2022
Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors
Jeffrey B Wyckoff1, Yarong Wang, Elaine Y Lin
1Gruss Lipper Center for Biophotonics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. jwyckoff@aecom.yu.edu
Abstract:
Although the presence of macrophages in tumors has been correlated with poor prognosis, until now there was no direct observation of how macrophages are involved in hematogenous metastasis. In this study, we use multiphoton microscopy to show, for the first time, that tumor cell intravasation occurs in association with perivascular macrophages in mammary tumors. Furthermore, we show that perivascular macrophages of the mammary tumor are associated with tumor cell intravasation in the absence of local angiogenesis. These results show that the interaction between macrophages and tumor cells lying in close proximity defines a microenvironment that is directly involved in the intravasation of cancer cells in mammary tumors.
Insights
Perivascular macrophages in mammary tumors directly facilitate cancer cell intravasation, a key step in hematogenous metastasis. This interaction occurs even without new blood vessel growth, revealing a novel mechanism in cancer spread.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Macrophages are known to correlate with poor cancer prognosis.
- The precise role of macrophages in hematogenous metastasis has remained unclear.
Purpose of the Study:
- To directly observe and elucidate the role of macrophages in tumor cell intravasation.
- To investigate the association between perivascular macrophages and cancer cell metastasis in mammary tumors.
Main Methods:
- Utilized advanced multiphoton microscopy for in vivo imaging.
- Observed interactions between tumor cells and perivascular macrophages within mammary tumors.
Main Results:
- Directly visualized tumor cell intravasation occurring alongside perivascular macrophages.
- Demonstrated this association in the absence of local tumor angiogenesis.
- Identified a tumor microenvironment shaped by macrophage-tumor cell proximity critical for intravasation.
Conclusions:
- Perivascular macrophages play a direct, crucial role in facilitating cancer cell intravasation.
- Macrophage-tumor cell interactions create a microenvironment promoting metastasis, independent of angiogenesis.

