Expression of tetraspanin adaptor proteins below defined threshold values is associated with in vitro invasiveness of mammary carcinoma cells

Sauer, Georg; Kurzeder, Christian; Grundmann, R; Zeillinger, Robert; Deissler, Helmut

doi:10.3892/or.10.2.405

Cited by 29 publications

(31 citation statements)

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“…TM4SF1) previously reported by our laboratory (11) and the plasmolipin gene previously reported by Pass et al (12). In other studies, low expression of CD9 is thought to contribute to a more aggressive (metastatic) phenotype in small cell lung cancer (19), gastric cancer (20), and breast cancer (21). These observations are generally consistent with our finding of CD9 expressed at significantly higher levels in tumors from patients with relatively good prognosis.…”

Section: Discussionsupporting

confidence: 83%

Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma

Gordon¹,

Rockwell

Godfrey³

et al. 2005

Clinical Cancer Research

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Purpose: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme. Experimental Design: Gene expression data using high-density oligonucleotide microarrays (f22,000 genes) were obtained for a new cohort of human MPM tumors from patients undergoing similar treatments (n = 39). The relative expression levels for specific genes were also determined using real-time quantitative reverse transcription-PCR. We also used a subset of these tumors associated with widely divergent patient survival (n = 23) as a training set to identify new treatment-specific candidate prognostic molecular markers and gene ratio^based prognostic tests. The predictive nature of these newly discovered markers and gene ratiob ased prognostic tests were then examined in an independent group of tumors (n = 52) using microarray data and quantitative reverse transcription-PCR. Results: Previously described MPM prognostic genes and gene ratio^based prognostic tests predicted clinical outcome in 39 independent MPM tumor specimens in a statistically significant manner. Newly discovered treatment-specific prognostic genes and gene ratio^based prognostic tests were highly accurate and statistically significant when examined in an independent group of 52 tumors from patients undergoing similar treatment. Conclusions:The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM.

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Section: Discussionsupporting

confidence: 83%

Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma

Gordon¹,

Rockwell

Godfrey³

et al. 2005

Clinical Cancer Research

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“…In breast cancer, CD9 down-regulation was correlated with nodal metastasis and decreased survival (8,22,30). We observed reduced or absent CD9 expression in 77 of 97 breast carcinomas, and this was not correlated with other tumor characteristics, including nodal involvement, nor was there a statistically significant relationship with Kai1 expression, which is in agreement with a previous report using quantitative reverse transcription-PCR (31). Although our CD9 down-regulation rate (79%) is higher than that in the Japanese series reported by Huang et al (33%), we are confident that our finding does not represent an artifact of paraffin section immunohistochemistry, because admixed benign cells always were strongly positive.…”

Section: Discussionsupporting

confidence: 82%

“…Clearly, abnormal expression of cell surface markers is common in human breast cancer and likely has profound pathophysiologic consequences. Similar conclusions were reached by Sauer et al who studied the expression of four tetraspanins (including Kai1 and CD9) in breast cancer cell lines (31). The current report introduces a few new players in the complex game of cell-cell and cell-matrix interactions, and some of them may well prove to play an important role in the development of mammary tumors.…”

Section: Discussionsupporting

confidence: 68%

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

Huang¹,

Groth²,

Sossey‐Alaoui

et al. 2005

Clinical Cancer Research

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Purpose: In a previous gene expression array study, we identified some 300 genes that were differentially expressed in human epidermal growth factor receptor tyrosine kinase 2 (HER2)p ositive versus HER2-negative breast cancer cells.We have now done validation experiments on a group of three cell membrane components that had previously not been implicated in breast cancer.We also studied the expression of three other cell membrane proteins known to play a role in mammary neoplasia. Experimental Design: By immunohistochemistry, we examined up to 130 archival breast carcinomas for Celsr2, E-cadherin, Kai1, and CD9 expression. The expression levels of NET-6 and TROP-2 were determined by quantitative reverse transcription-PCR in a subset of frozen tumors. We also studied fresh pellets and paraffin-embedded cell buttons of nine human breast cell lines. The relationship between the expression of all six membrane proteins and a variety of pathologic and biological variables, including estrogen receptor, HER2, and epidermal growth factor receptor status, was also examined. The NET-6 gene was transfected into a low-expressing cell line, and the effect on cellular morphology, growth, and invasion in vitro was recorded. Results: Celsr2 was down-regulated in one cell line and in 7% of breast cancers. E-cadherin, Kai1, and CD9 were down-regulated in 35%, 76%, and 79% of tumors, respectively, confirming the important role of these markers in human mammary neoplasia. In breast cancer cell lines and tissues, TROP-2 was generally expressed at low levels, although a few specimens showed relative overexpression. NET-6 levels were lower in HER2-negative breast carcinoma cells. In addition, NET-6 was markedly down-regulated in estrogen receptor^negative breast cancers, and expression was lowest in ''basal-like'' tumors. Ectopic expression of NET-6 in low-expressing MDA-MB-231cells altered cellular morphology, inhibited growth in vitro, and decreased invasion in a Boyden chamber assay. Conclusions: We have confirmed the expression of three new membrane markers that had previously not been implicated in human breast cancer, and one of them (NET-6) was correlated with HER2 and estrogen receptor status. NET-6 levels were decreased in estrogen receptor^negative and high-grade tumors, and ectopic expression of this gene had an inhibitory effect on proliferation and invasion. Thus, NET-6 may represent a novel breast cancer suppressor gene.

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“…Indeed, its expression is reduced in metastatic melanomas as compared to melanoma precanceroses (Kondoh et al, 1993), and its experimental overexpression suppresses malignancy of human melanoma cells or H-ras-transformed NIH3T3 murine cells (Hotta et al, 1991;Radford, Mallesch, & Hersey, 1995). In breast cancer cells, one report similarly indicates a significant negative correlation between CD63 mRNA level and in vitro invasiveness (Sauer et al, 2003).…”

Section: The Tetraspanin Cd63mentioning

confidence: 69%

The potentials of MS‐based subproteomic approaches in medical science: The case of lysosomes and breast cancer

Journet

Ferro

2004

Mass Spectrometry Reviews

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Because of the great number of women who are diagnosed with breast cancer each year, and though this disease presents the lowest mortality rate among cancers, breast cancer remains a major public health problem. As for any cancer, the tumorigenic and metastatic processes are still hardly understood, and the biochemical markers that allow either a precise monitoring of the disease or the classification of the numerous forms of breast cancer remain too scarce. Therefore, great hopes are put on the development of high-throughput genomic and proteomic technologies. Such comprehensive techniques should help in understanding the processes and in defining steps of the disease by depicting specific genes or protein profiles. Because techniques dedicated to the current proteomic challenges are continuously improving, the probability of the discovery of new potential protein biomarkers is rapidly increasing. In addition, the identification of such markers should be eased by lowering the sample complexity; e.g., by sample fractionation, either according to specific physico-chemical properties of the proteins, or by focusing on definite subcellular compartments. In particular, proteins of the lysosomal compartment have been shown to be prone to alterations in their localization, expression, or post-translational modifications (PTMs) during the cancer process. Some of them, such as the aspartic protease cathepsin D (CatD), have even been proven as participating actively in the disease progression. The present review aims at giving an overview of the implication of the lysosome in breast cancer, and at showing how subproteomics and the constantly refining MS-based proteomic techniques may help in making breast cancer research progress, and thus, hopefully, in improving disease treatment.

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Expression of tetraspanin adaptor proteins below defined threshold values is associated with in vitro invasiveness of mammary carcinoma cells

Cited by 29 publications

References 0 publications

Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma

Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

The potentials of MS‐based subproteomic approaches in medical science: The case of lysosomes and breast cancer

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