Factors that emerge as crucial participants in tumour invasion and metastases are matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase (TIMP) inhibitors and cellular adhesion molecules (CD44 and similar molecules).
In combination, the CD44(+)/CD24(-) phenotype was associated with the most favourable outcome (84 and 80% 10 year breast cancer survival [BCSS] and metastasis free survival [MFS], respectively).
We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44(+) subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression.
Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumors and the expression of specific CD44 isoforms (splice variants) has been shown to be associated with metastasis and poor prognosis in human malignancies.
Alternative splicing of CD44 and aberrant levels of soluble CD44 variants in the serum of cancer patients have been correlated to tumor progression and metastasis in different tumors including breast cancer.
Furthermore, p53 suppresses CD44 expression and the acquisition of stem cell-like properties responsible for epithelial to mesenchymal transition (EMT) and metastasis.
CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors.
In this study, a CD44 and N-cadherin dual targeting drug delivery system based on mesoporous silica nanoparticles (MSNs) has been successfully constructed for inhibiting tumour cell invasion and metastasis.
To test whether endothelial cells (ECs) associated with lung metastases express a distinct gene expression program that promotes metastatic growth, we isolated CD31<sup>+</sup>/CD45<sup>-</sup> cells from lung mammary cancer metastases for RNA sequencing and found CD44 upregulation.
Here, we report on the development of a new CD44-targeted copolymer carrying multiple copies of the A5G27 peptide, known for its ability to bind specifically to CD44v3 and CD44v6 on cancer cells and inhibit tumor cell migration, invasion, and angiogenesis.
To investigate if human tumours display altered CD44 expression we performed reverse transcriptase a polymerase chain reaction (PCR) analysis of CD44 in 49 specimens from normal colonic mucosa, primary colon and rectal tumours, normal liver, and metastases of 20 patients.
Furthermore, Asp-UA (80 mg/kg) reduced lung metastasis in a 4T1 murine breast cancer metastasis model more efficiently, which was associated with a decrease in the expression of CD44.
CD44 is considered as 'a' metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing.
For example, AF1q has been shown to interact with T-cell Factor 7 (TCF7; also known as TCF1) from the Wnt/β-catenin pathway resulting in the transcriptional activation of the CD44 and the enhancement of breast cancer metastasis.
Perlecan, a heparan sulfate proteoglycan of basement membranes and cell surfaces, has been implicated in the control of tumor cell growth and metastasis because of its ability to bind and store growth factors and its activity as an inducer of angiogenesis.
HMD CAL 51 produced more hyaluronidase (12-fold) and HA (10-fold) and expressed more CD44 (1.6-fold) and other HA-binding sites (9.5-fold) than the established cell line CAL 51.Our results show that i.p. injection of the CAL 51 cell line into nude mice provides a useful model of metastasis formation.