Annexin VII as a Novel Marker for Invasive Phenotype of Malignant Melanoma

Abstract

Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. While examining the genetic difference between the two sublines, we found a marked reduction of annexin VII expression in BL6 cells. In addition, fusion cell clones of both sublines were as poorly metastatic as F10 cells after subcutaneous injection, and contained the annexin VII message as abundantly as F10 cells. Hence, we examined whether the annexin VII expression was correlated with the less malignant phenotype of clinical cases by immunohistochemistry. Immunoreactivities to anti-annexin VII antibody in melanoma cells were evaluated quantitatively by using skin mast cells as an internal positive control. Eighteen patients with malignant melanoma were divided into two groups: lymph node metastasis-negative and positive groups. The ratio of numbers of patients positive versus negative to the antibody was significantly larger in the former than in the latter group. These results not only indicated that annexin VII serves as a marker for less invasive phenotype of malignant melanoma, but also suggested a possible role of annexin VII in tumor suppression. Key words: B16 melanoma -Ca 2+ -binding protein -Fusion cells -ImmunohistochemistryAn increasing number of people are suffering from malignant melanoma in various areas of the world. The major cause of death in the patients with melanoma is tumor metastasis. Several approaches, including immunologic examination, 1-3) single strand conformation polymorphism (SSCP), 4,5) and serological tumor markers, [6][7][8] have been applied to evaluate the metastatic potentials of melanoma cells. Immunohistochemistry is one of the simplest and most commonly used methods. However, few probes have been identified that serve as prognostic markers of malignant melanoma in immunohistochemistry. To seek a novel and useful prognostic marker, we have examined a variety of sublines of B16 mouse melanoma cells, which possess distinct metastatic potentials.9) The BL6 subline is one of the most malignant and is metastatic after both intravenous and subcutaneous injection, whereas F10 cells are metastatic only after intravenous injection.10, 11) The F1 subline is a parent of F10 cells and is poorly metastatic even after intravenous injection. 12)Previously, we determined the genetic dominance in the metastatic phenotype between F10 and F1 cells. Fusion cell clones of both cells were as highly metastatic after intravenous injection as F10 cells. High metastatic phenotype appeared to dominate in crosses between F1 and F10 cells. 13) In the present study, we determined the genetic dominance in the metastatic phenotype between F10 and BL6 cells, and found that the low metastatic phenotype was dominant in their crosses. This indicated that F10-derived metastasis-suppressive activity dominated over the BL6-derived metastasis-promoting activity. It is logical that factors essential for metastasis-suppressive activity are expressed in F...

Annexin-1 downregulation in thyroid cancer correlates to the degree of tumour differentiation

“…[29][30][31][32][33] These annexins are often linked with negative regulation of cell proliferation. 1 Annexins are commonly dysregulated in cancers 10 and their frequent downregulation has suggested a possible homeostatic or tumor suppressor role.…”

“…3,5,[9][10][11][12] ANXA2 is overexpressed in brain glial tumors 13 and pancreatic carcinoma, 14 but downregulated in prostate cancer. 15 Possible tumor suppressor role have been proposed for ANXA6 in melanoma 16 and squamous cell carcinoma, 17 for ANXA7 in melanoma, 18 and for ANXA10 in hepatocellular carcinoma. 19 Finally, ANXA4 has been associated with chemoresistance.…”

ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

“…Although ANXA7 was present in malignant neoplasms such as melanosome secreting melanoma or exosome secreting 51 mesothelioma (17% and 44%, respectively), it was previously shown to be a marker for less invasive phenotype in melanoma 52 consistent with its tumor suppressor role.…”

Down-Regulation of Annexin A10 in Hepatocellular Carcinoma Is Associated with Vascular Invasion, Early Recurrence, and Poor Prognosis in Synergy with p53 Mutation

“…25 In contrast, ANXA6 has tumor suppressive activity in squamous cell carcinoma, 26 and a decrease in ANXA6 and ANXA7 proteins is associated with malignant phenotype and the metastatic potential of melanoma. 27,28 Moreover, ANXA4 plays a role in chemoresistance. 29 Hence, there are at least two categories of ANXs implicated in tumor progression and tumor suppression, and different ANXs play important and complex roles in cancer.…”