Related Experiment Videos
Augmentation of B16 melanoma lung colony formation in C57BL/6 mice having marked granulocytosis
Abstract:
The effect that polymorphonuclear leukocytes (PMN) may have on the metastatic colonization of tumor cells is controversial: some laboratories have reported that PMN can inhibit metastasis whereas others have shown an augmentation effect. We have exploited our finding that a particular fibrosarcoma (BMT-11) transplanted subcutaneously into syngeneic C57BL/6 mice induces a progressive increase in the number of circulating PMN, to re-examine this question. We used such "granulocytosis-positive" mice as recipients of B16 melanoma cells to examine the influence of significant granulocytosis on the level of lung tumor colonies. The number of B16 melanoma lung colonies detected after intravenous (i.v.) injection was significantly higher in BMT-11 tumor-bearing mice with granulocytosis than in control (non-tumor-bearing) mice. Retention of 125IUdR-labelled B16 cells 24 hr after the i.v. injection was 3 to 10 times greater in mice with granulocytosis than in controls. Either simultaneous injection, or preinjection of PMN with B16 cells, increased the lung-colonizing capacity of B16 melanoma cells. These results suggest that abnormally increased numbers of PMN in the peripheral blood, particularly in the lung circulation, can enhance the ability of tumor cells to colonize or metastasize.
Insights
Elevated polymorphonuclear leukocytes (PMN) levels significantly increase tumor cell metastasis to the lungs. This study shows granulocytosis enhances cancer cell colonization, suggesting PMN play a role in cancer spread.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis
Background:
- The role of polymorphonuclear leukocytes (PMN) in cancer metastasis is debated, with conflicting reports on whether they inhibit or promote tumor spread.
- Previous research shows varying effects of PMN on metastasis, necessitating further investigation into their precise influence.
Purpose of the Study:
- To investigate the impact of induced granulocytosis on the metastatic colonization of tumor cells in a syngeneic mouse model.
- To re-examine the controversial role of PMN in cancer metastasis using a specific fibrosarcoma-induced granulocytosis model.
Main Methods:
- Utilized a syngeneic mouse model (C57BL/6 mice) with a fibrosarcoma (BMT-11) that induces progressive granulocytosis (increased circulating PMN).
- Administered B16 melanoma cells intravenously to control and granulocytosis-positive mice to assess lung colonization.
- Quantified lung tumor colonies and measured the retention of radiolabeled B16 cells in the lungs.
Main Results:
- Mice with BMT-11 induced granulocytosis exhibited a significantly higher number of B16 melanoma lung colonies compared to control mice.
- The retention of intravenously injected B16 melanoma cells in the lungs was 3 to 10 times greater in mice with granulocytosis.
- Simultaneous or prior injection of PMN with B16 cells enhanced the lung-colonizing capacity of the tumor cells.
Conclusions:
- Abnormally high levels of circulating PMN, particularly in the lung vasculature, can enhance tumor cell metastasis.
- These findings suggest that PMN contribute to the metastatic process by facilitating tumor cell colonization in the lungs.