Recent advances in pancreatic cancer: biology, treatment, and prevention

Singh, Divya; Upadhyay, Ghanshyam; Srivastava, Rakesh K.; Shankar, Sharmila

doi:10.1016/j.bbcan.2015.04.003

Cited by 70 publications

(95 citation statements)

References 214 publications

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“…Preferential target organs for metastasis are the liver, peritoneum and the lungs (97). Therefore, models which recapitulate early steps of pathogenesis of PDAC might be useful for diagnostic and therapeutic purposes.…”

Section: Metastatic Niche Of Pancreatic Carcinoma In the Livermentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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Section: Metastatic Niche Of Pancreatic Carcinoma In the Livermentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

View full text Add to dashboard Cite

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“…Pancreatic cancer is the fourth leading cause of cancer mortality in the United States (1,2). Although efforts to reduce risk factors such as smoking, obesity, and high meat consumption and to improve early detection have been made, pancreatic cancer is still formidable because of its aggressive metastatic ability (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

Chijiiwa

Moriyama

Ohuchida

et al. 2016

International Journal of Oncology

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Abstract.Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P= 0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer.

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“…In addition, our previous findings revealed that the activation of Notch4 promoted GC cell growth in vitro and in vivo, while the inactivation of Notch4 by siRNA had the opposite effects (6). In the present study, it was demonstrated Notch expression in PC was correlated with serosal invasion, lymph node metastasis, histopathological grading, tumor-node-metastasis stage and recurrence (21)(22)(23)(24). Enhanced Notch4 expression in salivary adenoid cystic carcinoma may stand as a novel mechanism for promoting metastasis (25).…”

Section: Discussionmentioning

confidence: 50%