Part of the multiple myeloma-associated microvessels is functionally connected to the systemic circulation: a study
Hendrik R De Raeve1, Kewal Asosingh, Eddie Wisse
1Department of Pathology, University of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. Hendrik.De.Raeve@uza.be
Abstract:
It is now well established that angiogenesis in multiple myeloma (MM) is associated with poor prognosis. The exact function of the newly formed vessels in MM is, however, a matter of debate. It is believed that, in contrast to solid tumor growth, the bone marrow (BM) is a sufficiently vascularized organ to support expansion of the MM clone with no need for additional blood vessels. From this point of view, it could be that MM-associated angiogenesis is rather an epiphenomenon and that the newly formed microvessels form a chaotic network that does not contribute to the blood flow. We investigated whether these newly formed microvessels in MM are connected to the blood circulation. The intravenously injected ferritin 30 min prior to sacrifice was detected in 100% of the BM vessels of control mice. In MM-bearing mice, the ferritin tracer was found in 31% of the MM-associated vessels, indicating a connection with the peripheral blood circulation in these vessels. We conclude that, comparable to the situation in solid tumors, at least part of the tumor-associated microvessels in MM is functionally connected to the blood circulation and, therefore, can participate in the transport of nutrients and in the dissemination of MM cells.
Insights
Newly formed blood vessels in multiple myeloma (MM) are connected to circulation. This suggests these vessels support tumor growth and spread, unlike previously thought for this cancer.
Area of Science:
- Hematology
- Oncology
- Vascular Biology
Background:
- Angiogenesis in multiple myeloma (MM) correlates with poor prognosis.
- The functional role of newly formed vessels in MM remains debated.
- The bone marrow's inherent vascularization was thought sufficient for MM growth.
Purpose of the Study:
- To investigate the functional connection of MM-associated microvessels to the blood circulation.
- To determine if newly formed vessels in MM contribute to blood flow.
Main Methods:
- Intravenous injection of ferritin tracer in control and MM-bearing mice.
- Detection of ferritin in bone marrow (BM) vessels post-sacrifice.
- Quantification of tracer presence in MM-associated vessels.
Main Results:
- Ferritin was detected in 100% of BM vessels in control mice.
- In MM-bearing mice, 31% of MM-associated vessels contained the ferritin tracer.
- This indicates a functional connection to peripheral blood circulation.
Conclusions:
- A portion of MM-associated microvessels are functionally integrated with the circulatory system.
- These connected vessels can facilitate nutrient delivery to the myeloma clone.
- Connected microvessels may also play a role in the dissemination of MM cells.
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