Related Experiment Video
Updated: May 30, 2026
A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
CD44 and HCELL: preventing hematogenous metastasis at step 1
Pieter P Jacobs1, Robert Sackstein
1Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Despite great strides in our knowledge of the genetic and epigenetic changes underlying malignancy, we have limited information on the molecular basis of metastasis. Over 90% of cancer deaths are caused by spread of tumor cells from a primary site to distant organs and tissues, highlighting the pressing need to define the molecular effectors of cancer metastasis. Mounting evidence suggests that circulating tumor cells (CTCs) home to specific tissues by hijacking the normal leukocyte trafficking mechanisms. Cancer cells characteristically express CD44, and there is increasing evidence that hematopoietic cell E-/L-selectin ligand (HCELL), a sialofucosylated glycoform of CD44, serves as the major selectin ligand on cancer cells, allowing interaction of tumor cells with endothelium, leukocytes, and platelets. Here, we review the structural biology of CD44 and of HCELL, and present current data on the function of these molecules in mediating organ-specific homing/metastasis of CTCs.
Insights
Metastasis, the spread of cancer cells, is poorly understood. This review highlights how cancer cells use CD44 and hematopoietic cell E-/L-selectin ligand (HCELL) to home to specific organs, similar to leukocyte trafficking.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Metastasis causes over 90% of cancer deaths, yet its molecular drivers remain largely unknown.
- Understanding cancer cell metastasis is crucial for developing effective treatments.
- Circulating tumor cells (CTCs) appear to utilize normal leukocyte trafficking pathways to reach distant sites.
Purpose of the Study:
- To review the structural biology of CD44 and HCELL.
- To present current data on the function of CD44 and HCELL in CTC homing and organ-specific metastasis.
- To elucidate the molecular mechanisms underlying cancer metastasis.
Main Methods:
- Literature review focusing on structural biology and functional data of CD44 and HCELL.
- Analysis of existing evidence on selectin ligand function in cancer cell trafficking.
- Integration of knowledge on leukocyte and tumor cell homing mechanisms.
Main Results:
- CD44 is characteristically expressed on cancer cells.
- Hematopoietic cell E-/L-selectin ligand (HCELL), a CD44 variant, acts as a key selectin ligand on cancer cells.
- HCELL mediates interactions between tumor cells, endothelium, leukocytes, and platelets, facilitating organ-specific metastasis.
Conclusions:
- CD44 and HCELL play critical roles in the organ-specific homing of circulating tumor cells.
- Hijacking leukocyte trafficking mechanisms by cancer cells involves CD44 and HCELL.
- Further research into these molecules could reveal novel therapeutic targets for preventing cancer metastasis.
