In 4T1-luc metastatic breast cancer model in mice, Sap-EGFR/CD44-NGs exhibited significant inhibition of tumor metastasis to lung at a small dose of 3.33 nmol Sap equiv./kg.
Surprisingly, EPR and Dox combination significantly down-regulated the CD44 receptor expression which is the main contributing factor of tumor metastasis.
In contrast, loss of CD44 resulted in significant increase of tumor burden at several locoregional sites, including liver, and unleashed distant metastases to the thoracic cavity.
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.
CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use of these factors as biomarkers may improve the accuracy of the prediction of cancer metastases and prognosis.
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.
Mixed co-injections of TME-enriched CD44+/CD24low/- and CD44+/β1+ sub-populations generated metastases populated mostly by CD44+/CD24low/--derived cells.
We previously demonstrated that Glypican-5 (GPC5), one of the members of heparan sulfate proteoglycan, was a novel tumor metastasis suppressor in lung adenocarcinoma (LAC).
Furthermore, deguelin-treated tumors showed decreased the tumor metastasis related genes such as CD44, MMP2 and MMP9 at protein and mRNA levels and the content of CEA, SCC, NSE, CYFAR21-1.
CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs.
These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases.
We hypothesize that a developed cancer-targeted delivery system that combines CD44 siRNA with paclitaxel would successfully deliver its payload inside cancer cells, effectively induce cell death, and prevent metastases.
Targeted inhibition of lipogenic enzymes abolished expression of CD44, a transmembrane protein associated with metastases in several cancers including CRC.
In addition, 2-D DIGE and HPLC/MS-MS of HER2(+)/CD44(+)/CD24(-/low) versus HER2(-)/CD44(+)/CD24(-/low) BCSCs reported a unique HER2-associated protein profile including effectors involved in tumor metastasis, apoptosis, mitochondrial function, and DNA repair.
When inoculated subcutaneously into NOD/SCID animals, the CD44 negative cells were capable of tumor formation and organ infiltration, clearly demonstrating an inverse correlation of CD44 expression and neuroblastoma metastases formation.
CD44 is a cell-surface glycoprotein involved in many cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis and tumor metastasis, suggesting that CD44 may play an important role in breast cancer development.