The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8 + and CD4 + T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. (Cancer Sci 2007; 98: 1652-1658) C hemokines are a family of small (8-14 kDa), mostly basic, heparin-binding cytokines that primarily induce directed migration of various types of leukocytes through interactions with a group of seven transmembrane G protein-coupled receptors (GPCR). GPCR mediate biological effects such as cell migration. That is, normal rapid leukocyte trafficking is controlled strictly by chemokines and their receptors.(1,2) To date, over 50 chemokines and 20 chemokine receptors have been identified, and are grouped into four categories (C, CC, CXC, and CX3C) based on the location of the main cysteine residues near the N termini of these proteins.Leukocyte trafficking and, to a lesser degree, cancer metastasis have regular rules called organ selectivity. The cancer metastatic process can be divided into several migration steps. First, cancer cells are released from the primary cancer to the surrounding tissues, enter the vascular or lymphatic circulation, and are transported through it. Then, the cells become arrested in the capillary bed of a distant organ and extravasate from the circulation to organ parenchyma. However, although cancer migration from the primary site to distant organs is essential to establish metastasis, we know very little about the molecular mechanisms that regulate cancer cell migration.It is now thought that chemokines play a significant role in organ-selective cancer metastasis, because cancer cell migration and metastasis share many similarities with leukocyte trafficking. (3,4) Several chemokine receptors are regarded as molecules related to cancer metast...

The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancers and has also been shown to participate in the development of cancer metastasis. The present study was carried out to assess immunohistochemically the pattern of CXCR4 expression in patients with metastatic prostate cancer. We analyzed whether there may be an association between CXCR4 expression and prognosis. Fifty-two patients who received hormonal therapy were enrolled. Specimens were obtained from transperineal needle biopsy before treatment, and were stained with antihuman CXCR4 antibody. We also evaluated the pathological grade, extent of bony metastasis, clinical response to hormonal therapy, and patient prognosis. CXCR4 was detected in 94.2% patients. Its expression showed no association with pathological grade, extent of bony metastasis, or clinical response to hormonal therapy. Patients with a high expression of CXCR4 in tumors had poorer cancer-specific survival than those with low expression of CXCR4. CXCR4 expression is a useful prognostic factor for patients with metastatic prostate cancer treated with androgen-withdrawal therapy. (Cancer Sci 2008; 99: 539-542)

The male reproductive functions of the members of the Masherbrum (7821 m) Expedition in 1999 were examined via semen analyses and endocrine tests. Specimens were collected from three subjects who had stayed above 5100 m for 21 to 24 days and above 6700 m for 4 to 5 days before departure and 1 month, 3 months, and 2 yr after returning from the expedition. Semen analyses showed no change in the semen volume. Sperm counts decreased after 1 month and had not recovered after 3 months, but they had recovered after 2 yr in all subjects. An increase in abnormally shaped sperm was also observed after 1 month, but had nearly recovered to the preexpedition state after 3 months. Endocrine tests revealed slightly decreased testosterone in the blood after 1 month, which had decreased still further after 3 months. The tests were completely normal after 2 yr. We suggest that a high altitude sojourn may induce reversible spermatogenic and Leydig cell dysfunction.

No abstract

No abstract

1 AbstractThe specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH 2 -terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the G α13 and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development.Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa.

We previously reported that androgen receptor (AR) plays a role in the regulation of adhesion to the extracellular matrix and invasion of human prostate cancer cells by influencing the expression of specific integrin subunits. It is now considered that chemokines play a significant role in organ-selective cancer metastasis. In this study, we hypothesized that AR may influence the expression of these chemokine receptors and cell function. The mRNA expression of chemokine receptors in human prostate cancer cell line DU-145 and DU-145 cells expressing AR (DU-145/AR) was investigated by RT-PCR. DU-145 cells selectively expressed CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed vigorous migratory responses to its ligand CXCL12 (also called stromal-derived factor-1•, SDF-1•) and CCL3 (also called macrophage inflammatory protein-1, MIP-1•). In contrast, neither CXCL12 nor CCL3 affected the migration of DU-145/AR cells. These results indicate that expression of AR down-regulates the migratory responses of human prostate cancer cells via chemokine and its receptor systems.

Eighty-one fresh semen samples were analyzed to compare the sperm parameters obtained using the new Sperm Motility Analysis System (SMAS; version 1.0, Kaga Electronics, Tokyo, Japan) with the CellSoft TM Series 3000(CRYO Resources, New York, USA) computer-assisted semen analysis (CASA) system and conventional manual semen analysis, based on WHO guidelines.. Significant correlations of sperm concentration (po0.0001) and sperm motility (po0.0001) were observed between SMAS and manual semen analysis estimates. There were also significant correlations of sperm concentration (p ¼ 0.0003) and sperm motility (po0.0001) between SMAS and CellSoft estimates. Significant correlations for motility-related parameters were demonstrated in sperm velocity (po0.0001), and linearity (linear velocity (VSL) divided by curvilinear velocity (VCL) Â 100) (po0.0001), amplitude of lateral head displacement (ALH) (po0.0001), and beat/cross frequency (BCF) (p ¼ 0.0127), between SMAS and CellSoft estimates. In this study, we showed the usefulness of the new SMAS, which has high reliability in estimating sperm concentration, sperm motility, velocity and linearity compared with CellSoft. SMAS can be a promising alternative, providing costeffective semen analysis with the utility of the CASA system.