Elsevier

Oral Oncology

Volume 40, Issue 2, February 2004, Pages 154-157
Oral Oncology

Investigation of CXCR4 in squamous cell carcinoma of the tongue

https://doi.org/10.1016/S1368-8375(03)00144-1Get rights and content

Abstract

Cancer metastasis is not a random process and different cancer types have favorite metastatic sites. Recent studies on metastasis have focused on chemoattraction, particularly on the role of chemokines. Therefore, in this study we investigated whether CXCR4 (receptor for stromal cell-derived factor-1) is expressed in squamous cell carcinoma of the tongue. For this purpose, immunohistochemical staining was performed on 26 sections obtained from 23 patients (15 patients having tongue tumor without lymph node metastasis and eight patients having lymph node metastasis). All tumor cells expressed CXCR4, whereas normal mucosa of the tongue had no or faint expression CXCR4. Metastatic tumor cells in lymph nodes had stronger expression than primary tongue tumor cells. Our data raises the possibility that CXCR4 could be involved in lymph node metastasis of oral squamous cell carcinoma.

Introduction

The overwhelming preponderance of oral cavity cancers is squamous cell carcinoma (SCC). Cancer of the tongue comprises nearly 50% of all intraoral cancers. About half of patients with advanced cancer (UICC Stage III or IV) die within 5 years and the most important prognostic factor is the presence of lymph node metastasis.1 Cancer metastasis is the result of many sequential steps and is not a random process. Different cancer types have their own favorite sites for metastasis.2, 3 Though there are a number of molecules that have been shown to play a role in the metastatic process, the exact mechanisms determining the directional migration and invasion of tumor cells into specific organs have not been clearly established yet.

Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that selectively attract and activate different cell types. There are many patho-physiological conditions that chemokines involve such as inflammation, tissue injury, allergy, infection, cardiovascular diseases and malignant tumors.2, 4, 5 Muller et al. 3 investigated the expression of chemokines and their receptors in breast cancer patients to find out whether metastatic breast cancer cells were responsive to gradients of chemotactic chemokines. They found that CXCR4 was highly expressed in malignant breast cancer and its ligand stromal cell-derived factor-1 (SDF-1) was expressed in those organs, including regional lymph nodes, where breast cancer metastases are frequently seen.

We hypothesized that, oral tumor cells may use chemokine-mediated mechanisms during the process of metastasis. For this purpose, we performed immunohistochemical analysis to search the expression of CXCR4 in SCC of the tongue.

Section snippets

Patient population

Our patient population consisted of 23 patients (13 male and 10 female, age ranged 33–82 years with a median of 57 years) with tongue SCC. Of the 23 patients, 10 (43.5%) had Stage I disease (UICC), 5 (21.7%) had Stage II, 3 (13%) had Stage III, and 5 (21.7%) had IV. Five (21.7%) initially had lymph node metastasis, and four (17.4%) had delayed lymph node metastasis. Patients undergoing preoperative chemotherapy and/or radiation therapy were not included.

Specimen collection and preparation

All the specimens were collected

Results

All specimens demonstrated positive staining for CXCR4 on SCC cells, whereas normal squamous epithelium had negative to weak staining in cytoplasm (Fig. 1A). Small number of lymphocytes, constantly expressing CXCR4, was localized in the underlying layers of the normal epithelium, and strong staining for CXCR4 was detected on muscle cells of the tongue. Early Stage SCC cells expressed CXCR4 receptors (Fig. 1B). Numerous lymphocytes infiltrating in the surrounding connective tissues and tongue

Discussion

Tumor metastasis is the hallmark of malignancy, and is probably a result of the interaction between tumor cells and a supportive microenvironment. Malignant cells that have the capability to metastasize to a particular organ may have various properties supporting their tissue invasion or growth such as enhanced adherence to the microvascular cells of the organ, higher responsiveness to chemotactic signals released from the target organs and increased response to local soluble or tissue

Acknowledgements

This study was partially supported by The Osaka Medical Research Foundation for Incurable Diseases.

References (12)

There are more references available in the full text version of this article.

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