Accumulating evidence indicates that a small subset of
cancer cells, termed the tumor-initiating cells or cancer stem cells (CSCs), construct a reservoir of self-sustaining
cancer cells with the characteristic ability to self-renew and maintain the
tumor mass. The CSCs play an important role in the
tumor initiation, development, relapse,
metastasis, and the ineffectiveness of conventional
cancer therapies. CD47 is a
ligand for signal-regulatory
protein-α expressed on phagocytic cells and functions to inhibit phagocytosis. This study was to explore if the expression of CD47 is the mechanism used by
lung cancer cells, especially CSCs, to escape phagocytosis in vitro and in vivo. Here, we selected CD133 as the marker for lung CSCs according to previous reports. We analyzed
lung cancer and matched adjacent normal (non-
tumor) tissue and revealed that CD47 is overexpressed on
lung cancer cells, especially on lung CSCs. The
mRNA expression levels of CD47 and CD133 correlated with a decreased probability of survival for multiple types of
lung cancer. Blocking CD47 function with anti-CD47
antibodies enabled macrophage phagocytosis of
lung cancer cells and lung CSCs. Anti-CD47
antibodies inhibited
tumor growth in immunodeficient mouse
xenotransplantation models established with
lung cancer cells or lung CSCs and improved survival in
tumor-bearing animals. These data indicate that CD47 is a valid target for
cancer therapies, especially for anti-CSC
therapies.