Expression of CXCR4 Is Associated with Progression and Invasion in Patients with Nasal-Surface Basal Cell Carcinoma

Abstract

Background: Basal cell carcinoma (BCC) is the most common type of skin cancer with an increasing incidence worldwide that imposes a considerable burden on public health. C-X-C chemokine receptor (CXCR4) plays a vital role in initiation, progression and metastasis of several types of cancers. The aim of the present study was to investigate the expression and clinical significance of CXCR4 in BCC. Methods: In this study, 80 samples of primary BCC were assessed for CXCR4 expression using immunohistochemistry. The mRNA and protein expression levels of CXCR4 were evaluated by real-time reverse transcription polymerase chain reaction and Western blot analysis, respectively. Results: CXCR4-positive staining was detected in 70% of BCC samples. Overexpression of CXCR4 was significantly associated with tumor size (>2 vs. 2 cm, p = 0.002) and pathological type (invasive vs. noninvasive, p = 0.007). CXCR4 was also upregulated at transcriptional and translational levels. Conclusion: Our study revealed that the expression of CXCR4 was associated with progression and invasion in patients with BCC. It may be a considerable biomarker to assess invasiveness of nasal-surface BCC and to guide clinical management of such tumors.

The wound healing, chronic fibrosis, and cancer progression triad

“…In cancer, the SDF-1/CXCR4 axis has been implicated in the progression of several types of malignancies, and its expression is associated with poor prognosis (66,132,387,393,395). An important study almost a decade ago demonstrated that SDF-1 secreted by TAFs (but not normal fibroblastic cells) triggers both angiogenesis and tumor growth via CXCR4 (275).…”

CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

“…Due to the autocrine and paracrine CXCL12 secretion, the contradictory phenomenon remains to be further studied. In primary nasal-surface BCC tumor, upregulation of CXCR4 in normal skin tissues compared to normal skin tissues revealed that potential capacity of CXCR4 in progression and invasion of nasalsurface BCC [22]. Bazal et al demonstrated that BCC patients with deep tissue invasion showed signi cant high CXCR4 staining rate (75%) than patients with papillary dermis invasion (14.3%) [36].…”

“…ACC usually develops late-onset distant metastases, years after resection of the primary tumour [16]. The current study focuses on the CXCR4-CXCL12 axis as overriding molecular mechanism in distant metastatic outgrowth that was suggested to be associated with poor survival in BCC, HNSCC, MM, and ACC [17][18][19][20][21][22].…”

CXCR4 signalling, metastasis and immunotherapy: zebrafish xenograft model as translational tool for anti-cancer discovery

“…In cancer, malignant cells acquire higher CXCR4 levels, compared to normal tissues, and are found to preferentially metastasise in organs where CXCL12 is secreted, in line with the "seed and soil" theory [14] . Enhanced CXCR4 signalling has been identified in several malignancies such as gastrointestinal tumours [15] , melanoma [16] , basal cell carcinoma [17] , head and neck squamous cell carcinoma [18] , lung cancer [19] , breast [20] and ovarian [21] tumours, renal cell carcinoma [22] , prostate cancer [23] , glioblastoma multiforme (GBM) [24] , Ewing sarcoma [25] and leukemia [26] . Elevated CXCR4 levels result in increased cell proliferation, dedifferentiation, migration and metastatic spreading of tumour cells, cancer stem cell (CSC) maintenance and it has been associated with the development of tumour resistance towards conventional therapies, leading to poor patient prognosis [27] .…”