|
| Cancer | Comments | References |
|
| Acute lymphoblastic leukemia | Levels of CXCR4 are elevated on
lymphoblasts. Elevated levels of CXCR4 are associated with increased
infiltration in liver and spleen | [58] |
|
| Acute myelogenous leukemia | High CXCR4 expression is associated with relapse and reduced survival | [59] |
|
| Brain cancer | CXCR4 expression is demonstrated
in tissues and cell lines derived from glioblastoma, medulloblastoma, and
astrocytoma. Cell lines respond to CXCL12 with increased proliferation,
survival and migration. Gliomas expressing CXCR4 are associated with
increased tumor size and reduced survival | [41, 60–64] |
|
| Breast cancer | High CXCR4 expression is noted in breast cancer tissues compared to normal tissues and cell lines with invasive characteristics. CXCR4 expression is associated with more extensive lymph node metastasis and with liver metastasis, although CXCR4 expression in lymph node metastases may be lower than primary cancers. CXCR4 co-expression with HER2/neu is an indicator of more extensive lymph node involvement | [25, 28, 65–67] |
|
| Cervical cancer | CXCR4 expression is associated with increased tumor size, stromal invasion, lymph node metastasis, and reduced survival | [68] |
|
| Chronic lymphocytic leukemia | Malignant B cells express 3- to 4-fold higher cell-surface CXCR4 levels than normal B cells. High CXCR4 expression on B cells is associated with reduced survival in patients with familial chronic lymphocytic leukemia | [69, 70] |
|
| Colorectal cancer | CXCR4 is over-expressed in colorectal carcinoma tissues compared to normal tissues, and on certain established cell lines. In patients with liver metastasis, higher CXCR4 expression is found on liver metastases compared to the primary tumor. In patients with stage I/II disease, high CXCR4 mRNA expression in tumor samples is associated with increased disease recurrence. In patients with stage IV disease, patients with high CXCR4 have decreased overall survival. High CXCR4 expression is associated with increased lymph node involvement and distant metastasis, as well as reduced 3-year
survival | [40, 71–75] |
|
| Endometrial cancer | Endometrial adenocarcinoma
tissues and human cell lines express CXCR4 protein. CXCL12 induces proliferation of endometrial
carcinoma cells | [76] |
|
| Esophageal cancer | CXCR4 expression is associated
with reduced survival and increased lymph node/bone marrow metastasis | [77] |
|
| Gastric cancer | A majority of primary gastric tumors
and many human gastric carcinoma cell lines express CXCR4. Primary tumors
that express CXCR4 protein are associated with peritoneal carcinomatosis | [78] |
|
| Head and neck squamous cell
cancer | CXCR4 expression is found in
tissues and cell lines. High CXCR4 expression is associated with increased
occurrence of distant metastases and reduced survival | [79, 80] |
|
| Hepatocellular carcinoma | CXCR4 is correlated with tumor
progression, metastasis, and reduced survival | [81] |
|
| Melanoma | CXCR4 protein is expressed on
human melanoma cell lines, as well as on cells isolated from melanoma surgical
specimens. CXCL12 enhances cell
adhesion to fibronectin, the binding of murine melanoma cells to endothelial
cells, and invasion of human melanoma cells across basement membranes. CXCR4
expression is associated with reduced disease-free survival and overall
survival | [35, 43, 82, 83] |
|
| Multiple myeloma | Multiple myeloma cells isolated
from bone marrow and multiple myeloma cell lines express cell-surface CXCR4
protein. CXCL12 enhances adhesion to fibronectin and stimulates cell
migration | [84] |
|
| Nasopharyngeal cancer | Most primary human nasopharyngeal
carcinoma biopsy samples and metastatic lymph nodes stain positively for
CXCR4 protein. Nasopharyngeal carcinoma cell lines also express CXCR4 mRNA | [85] |
|
| Non-Hodgkin’s lymphoma | Most tissue samples and cell
lines express high levels of CXCR4 mRNA and cell-surface protein. CXCR4 is
implicated in transendothelial migration and proliferation of non-Hodgkin’s
lymphoma cells | [86] |
|
| Nonmelanoma skin cancer | CXCR4 is expressed on invasive
squamous cell carcinoma and basal cell carcinoma tissues. Expression on invasive squamous cell
carcinoma is increased compared to normal skin | [87] |
|
| Non-small cell lung cancer | CXCR4 mRNA is upregulated in
NSCLC tissues compared to normal tissues, and levels are higher in tissue
samples taken from patients with metastasis than from those without
metastasis. Overexpression of CXCR4 in
NSCLC cells leads to enhanced migratory, invasive, and adhesive responses to
CXCL12. Nuclear CXCR4 staining is
associated with longer survival and reduced incidence of metastasis | [88, 89] |
|
| Osteosarcoma | CXCR4 mRNA is expressed in most
human osteosarcoma samples, and two of three osteosarcoma cell lines. CXCR4
expression is higher at metastatic sites than in the primary tumor | [90, 91] |
|
| Ovarian cancer | CXCR4 mRNA is expressed in
ovarian cancer cell lines, as well as in biopsies from primary tumors and
ovarian cancer ascites. High levels of CXCL12 are present in ascitic fluid
taken from patients with ovarian cancer. CXCL12 stimulates the growth of
ovarian cancer cells. CXCR4 expression is associated with increased
recurrence and reduced survival | [26, 33, 92] |
|
| Pancreatic cancer | Most human pancreatic cancer
tissues stain positively for CXCR4 expression, and more than half of
pancreatic cancer cell lines express CXCR4 mRNA and cell-surface protein.
CXCL12 induces chemotaxis of human pancreatic carcinoma cells, as well as
stimulates proliferation and promoted survival | [42, 93] |
|
| Prostate cancer | Prostate cancer cell lines
express CXCR4 mRNA and protein, and approximately half of prostate cancer
tissues stain positively for CXCR4. Treatment of cells with CXCL12 increases
their adherence to osteosarcoma cells and bone marrow endothelial cells,
transendothelial migration, and invasion into Matrigel. CXCR4 expression is a
positive predictor of bone metastasis, particularly in patients with elevated
prostate specific antigen (PSA) levels. High CXCR4 expression is associated
with increased cancer-specific mortality | [29, 36, 94, 95] |
|
| Renal cell cancer | One of four human renal cell
cancer lines express CXCR4 mRNA, which is upregulated in renal cell cancer tumor
samples compared to normal tissue. High CXCR4 expression is associated with
poor tumor-specific survival, independent of tumour stage and differentiation
grade | [96, 97] |
|
| Rhabdomyo sarcoma | Several rhabdomyosarcoma cell
lines express cell-surface CXCR4 protein. CXCL12 increases cell motility,
induces chemotaxis, increases adhesion to extracellular matrix, and
stimulates secretion of MMP-2 | [37] |
|
| Small cell lung cancer | CXCR4 mRNA and cell-surface protein
are detected in cell lines. CXCL12 induces proliferation, increases adherence
and motility, and induces morphological changes such as filopodia formation | [98] |
|
| Thyroid cancer | Human thyroid carcinoma cell
lines express CXCR4 protein, and CXCR4 is upregulated in primary papillary
thyroid carcinomas compared to normal thyroid tissue. CXCL12 increases
proliferation, inhibits apoptosis, and increases migration and invasion of
human thyroid cancer cells | [99, 100] |
|
