How Are Breast Cancer Metastases Able to Survive and Grow in Draining Lymph Nodes?
Abstract
The goal of this project was to elucidate how breast cancer metastases manage to survive and grow in draining lymph nodes surrounded by highly immuno-reactive cells. In animal models, we have observed that while most lung metastases are susceptible to infiltration by lymphocytes, some metastases form very compact nodules that are hypovascular and contain very little extracellular matrix. These compact metastases are very resistant to lymphocytic infiltration. We therefore hypothesized that lymph node (LN) metastases, in order to resist attack by nearby lymphocytes, grow with this compact morphology. While our animal model of B16 melanoma LN metastases demonstrated that both type of metastases (i.e., compact and non- compact (called "loose") develops, metastases in four out of six positive nodes from breast cancer patients clearly exhibited the compact phenotype. Thus, we have found clear evidence that LN metastases in humans often grow with a compact morphology which, for yet unknown reasons, protects the metastases from lymphocytic infiltration. This may explain why the metastases are able to grow in the LN and we speculate that analysis of the metastases with respect to morphology (compact versus loose) may serve as a prognostic factor. Finally, we are investigating whether it will be possible to break the "stealth" of the compact metastases, allowing lymphocytes and dendritic cells to gain access to the malignant cells. We anticipate that better contact between tumor cells and dendritic cells/lymphocytes will lead to the induction of strong, anti-tumor responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407445
Entities
People
- Per H. Basse
Organizations
- University of Pittsburgh