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Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.

ABSTRACT: The targeting protein for Xklp2 (TPX2) has recently gained attention as a putative oncogene possibly amplified in several human malignancies, including pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to further explore the potential of TPX2 as a therapeutic target.The DNA copy number and expression of the TPX2 gene were surveyed in pancreatic cancer cell lines and tumor tissues and compared with those of immortalized normal pancreatic ductal cells and normal pancreatic tissues. The cellular effects of TPX2 knockdown using small interfering RNA oligonucleotides in pancreatic cancer cells, such as growth in tissue culture, in soft agar, and in nude mice; apoptosis; and sensitivity to paclitaxel, were also investigated using various assays.Low-copy-number TPX2 amplification was found in pancreatic cancer cell lines and low-passage pancreatic cancer tumor xenografts. TPX2 expression was upregulated in pancreatic cancer cell lines at both the mRNA and protein levels relative to the immortalized pancreatic ductal epithelial cell line HPDE6. Immunohistochemical staining of a tissue microarray showed that TPX2 expression was higher in pancreatic tumors compared with their normal counterparts. Treatment with TPX2 targeting small interfering RNAs effectively reduced pancreatic cancer cell growth in tissue culture, induced apoptosis, and inhibited growth in soft agar and in nude mice. Knockdown of TPX2 also sensitized pancreatic cancer cells to paclitaxel treatment.Our results suggest that TPX2 might be an attractive target for pancreatic cancer therapy.

SUBMITTER: Warner SL

PROVIDER: S-EPMC2783218 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.

Warner Steven L SL Stephens Bret J BJ Nwokenkwo Stanley S Hostetter Galen G Sugeng Anastasia A Hidalgo Manuel M Trent Jeffery M JM Han Haiyong H Von Hoff Daniel D DD

Clinical cancer research : an official journal of the American Association for Cancer Research 20091027 21

<h4>Purpose</h4>The targeting protein for Xklp2 (TPX2) has recently gained attention as a putative oncogene possibly amplified in several human malignancies, including pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to further explore the potential of TPX2 as a therapeutic target.<h4>Experimental design</h4>The DNA copy number and expression of the TPX2 gene were surveyed in pancreatic can ...[more]

PMID: 19861455

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.

Dataset Information

Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.

Publications

Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.

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