Prognostic role of CD44 expression in osteosarcoma: evidence from six studies

Yan²,

et al. 2018

Cell Physiol Biochem

Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B) and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.

Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 90%

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CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells

Yan²,

et al. 2018

Cell Physiol Biochem

“…In addition, although the mechanism remains unclear, CD44 and HA are both correlated with drug resistance [10]. Overall, CD44 is a potential prognostic marker for various diseases [48][49][50].…”

Section: Discussionmentioning

confidence: 97%

The prognostic value and clinicopathological significance of CD44 expression in ovarian cancer: a meta-analysis

Zhao

Zhang

et al. 2016

Arch Gynecol Obstet

High CD44s expression possibly indicates poor prognosis in OC patients given that high CD44s expression initiates chemotherapy resistance, although this expression pattern is not an independent predictive factor for OS. Meanwhile, high CD44s expression may be related to poor DFS of OC, but this relationship must be further confirmed. In addition, the result in which CD44v6 is not associated with OS of OC patients should be interpreted with caution.

“…It is considered to arise from malignant mesenchymal cells, which produce osteoid or immature bone (2). Although advanced treatment for osteosarcoma consists of aggressive adjuvant chemotherapy, the five-year survival rate of patients with high-grade osteosarcoma remains <50% (3).…”

Section: Introductionmentioning

confidence: 99%

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner

Molecular Medicine Reports

Qiao

Wang

et al. 2015

Abstract. Ubiquitin-like with plant homeodomain (PHD) and RING-finger domain 1 (UHRF1) maintains methylation patterns following DNA replication and is expressed at high levels in various types of human cancer. UHRF1 has been identified as a novel oncogene involved in the pathogenesis of hepatocellular carcinoma. Previous studies have demonstrated that inhibition of the expression of UHRF1 suppresses the proliferation of cancer cells. However, the role of UHRF1 in human osteosarcoma has not been investigated. The present study examined the expression levels of UHRF1 and retinoblastoma 1 (Rb1) in human osteosarcoma cell lines by western blot analysis. Stable overexpression of UHRF1 or knockdown of Rb1 was achieved by lentiviral transfection. Subsequently, a Cell Counting Kit-8 assay and a cell invasion assay were performed to detect the biological functions of UHRF1 in vitro. The results of the present study demonstrated that UHRF1 promoted the proliferation of human osteosarcoma cells. The present study also reported that UHRF1 was able to enhance the invasion of osteosarcoma cells in a retinoblastoma 1 (Rb1)-dependent manner. UHRF1 promoted invasion in Rb1-positive osteosarcoma cells, but not in Saos-2 cells with homozygous loss of Rb1. Similarly, knockdown of Rb1 in Rb1-positive osteosarcoma cells enhanced levels of invasion and eliminated the regulation of invasion by UHRF1. UHRF1 was found to inhibit the mRNA and protein expression levels of Rb1. Furthermore, deletion of Rb1 was found to suppress the expression of E-cadherin and promote epithelial-to-mesenchymal transition (EMT). In addition, the overexpression of UHRF1 inhibited the expression of E-cadherin and promoted EMT via the suppression of Rb1. These data demonstrated that UHRF1 promotes osteosarcoma cell invasion by downregulating the expression of E-cadherin and increasing EMT in an Rb1-dependent manner.