While reading an article, I came to know that RBCs cannot reach solid tumors. May I kindly know the reason behind?
VEGF-induced tumor angiogenesis is collapsed due to the ECM stiffness in several solid cancers such as pancreatic tumor. Collapsed tumor blood vessels do not let RBC reach the tumor tissue, while neutrophils and macrophages tend to extravasate and infiltrate into the tumor tissues.
Of course Dr Yoshida is correct and much of tumor vasculature is dysfunctional/leaky/ non-perfused/"pressure-sealed" by fibrotic stroma etc. However, I think you may be interested to know about the concept of vascular mimicry i.e. cancer cells forming vessel-like structures that "tap into" existing vessels to procure blood supply directly to and through the tumor mass, see e.g. http://www.nature.com/nm/journal/v17/n11/box/nm.2537_BX1.html. It is a debated concept but in my opinion, certain types of tumors were convincingly shown to utilize such a mechanism.
I would like to add the comment in terms of the metastatic-niche formation.
RBCs are rarely observed also in the pre-metastatic niche, where the lysyl oxidases (LOX) and LOX-like proteins (LOXL) secreted by primary cancer cells cause the bridging of collage, to promote the deposition of fibronectin, and to recruit CD11b-positive bone marrow-derived cells (BMDCs) under hypoxia. Of note, accumulation of fibronectin produced by fibroblasts and fibroblast-like cells has been reported to determine at which sites metastatic niches form, although at least some of the deposited fibronectin is derived from the primary tumor cells.
This remodeling of the tumor stroma makes “tumor stiffness,” which contributes to the collapsed tumor blood vessels in the metastatic site as well as primary site. The absence of RBCs which supply oxygen to the peripheral tissues results in the hypoxia of the tumor microenvironment and easily activate HIF1-alpha-mediated angiogenesis and remodeling the tumor stroma as previously mentioned.
Many thanks Sir!
I much appreciate these valuable and detailed comments.
Very interesting discussion. Therefore, the compromised entry of RBC to such tumor sites may be one important cause for the lack of oxygen, as Dr. Yoshida mentioned, and moreover, also to the acidification of the extracellular fluid where those cancer cells are growing.
