Abstract
CD24 is involved in tumor progression of various cancers, but the effects of CD24 on tumor angiogenesis in colorectal cancer are still unknown. We aimed to investigate the underlying mechanism and role of CD24 on colorectal cancer (CRC) angiogenesis. Our data showed that the microvessal density (MVD) was related to the expression of CD24 in primary and metastasis CRC. Silencing of CD24 could dramatically decrease human umbilical vein endothelial cell (HUVEC) migration, invasion and tubule formation, but trivially affected cell proliferation. We also mechanically showed that silencing CD24 could downregulate the expression of VEGF via inhibiting the phosphorylation and translocation of STAT3. Moreover, Hsp90 was identified as the down-interaction protein of CD24 with co-immunoprecipitation assay and systematic mass spectrometry. Immunofluorescence results showed Hsp90 partly co-localized with CD24 in CRC cell membrane and there was a positive correlation between CD24 and Hsp90 expression in CRC tissues. We gradually evidenced that Hsp90 modulated the stability and degradation of CD24 in a proteasome-depended manner, and transferred the signal transmission from CD24 to STAT3. 17-AAG, a specific Hsp90, could abrogate the CD24 induce- HUVEC migration, invasion and tubule formation in vitro and in vivo. Collectively, our results suggested that CD24 induced CRC angiogenesis in Hsp90-dependent manner and activated STAT3-mediated transcription of VEGF. We provided a new insight into the regulation mechanism of tumor angiogenesis by exploring the role of CD24 in angiogenesis.
Highlights
Human CD24 is a short mucin-like cell surface protein consisting of a small protein core linked to cytoplasm membrane raft domains through a glycosylphosphatidylinositol (GPI) anchor [1,2,3]
Our results showed that CD24 expression was closely related to microvessal density (MVD) in primary colorectal cancer tissue and liver metastasis tissue (Figure 1A, 1B)
Our results showed that CD24 affected human umbilical vein endothelial cell (HUVEC) migration, invasion, tubule formation and angiogenesis in vitro
Summary
Human CD24 is a short mucin-like cell surface protein consisting of a small protein core linked to cytoplasm membrane raft domains through a glycosylphosphatidylinositol (GPI) anchor [1,2,3]. Many studies have demonstrated that CD24 was overexpressed in most cancer cells and was closely related to the cancer cell proliferation, invasion and metastasis. CD24 was regarded as a poor prognosis marker in various cancer patients, such as breast cancer and colorectal cancer(CRC) [4]. This evidence suggested CD24 was an important oncogene in the colon tract. Angiogenesis is a pivotal event in tumor progression and metastasis. Salnikov AV et al found that the silencing CD24 with special mono-antibody inhibited the tumor cell proliferation and angiogenesis in vivo and in vitro [7]. We hypothesized that CD24 might play a key role in CRC angiogenesis
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