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![The Role of Inter-Alpha-Trypsin-Inhibitor-Heavy-Chain-5 (ITIH5) in Suppressing Pancreatic Cancer Metastasis için kapak resmi The Role of Inter-Alpha-Trypsin-Inhibitor-Heavy-Chain-5 (ITIH5) in Suppressing Pancreatic Cancer Metastasis için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
The Role of Inter-Alpha-Trypsin-Inhibitor-Heavy-Chain-5 (ITIH5) in Suppressing Pancreatic Cancer Metastasis
Başlık:
The Role of Inter-Alpha-Trypsin-Inhibitor-Heavy-Chain-5 (ITIH5) in Suppressing Pancreatic Cancer Metastasis
Yazar:
Young, Eric Douglas, author. (orcid)0000-0002-0014-1482
ISBN:
9780438024694
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (101 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Danny R. Welch Committee members: Nikki Cheng; Tim Fields; Tomoo Iwakuma; Roy Jensen; Russel Swerdlow; Danny Welch; Michael Wolfe.
Özet:
Metastasis is the spread of cancer from the site of origin to a distant site, where the colony of malignant cells grows. Growth of malignant cells in secondary sites disrupts organ function and increases the tumor burden on the host. Thus, there is a critical need to understand the factors regulating the spread of cancer cells to distant sites and their growth therein. Over half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) present with liver metastasis, and five-year survival for these patients is currently three percent. We performed an in vivo screen for PDAC metastasis suppressors using a human whole-genome shRNA library in order to understand factors regulating PDAC metastasis and identified Inter-alpha-Trypsin Inhibitor Heavy Chain 5 (ITIH5) as a suppressor of PDAC metastasis. Knockdown of ITIH5 significantly increased liver metastasis while high ITIH5 expression was correlated with rounded cell morphology and decreased cell motility and metastasis. ITIH5 is a secreted protein related to plasma protease inhibitors. To test the hypothesis that secretion of ITIH5 is required to suppress metastasis, we deleted the secretion signal sequence of ITIH5 (ITIH5?s) and compared development of liver metastasis in highly metastatic PDAC cells expressing either control vector, secreted ITIH5, or secretion-deficient ITIH5Deltas. Intriguingly, ITIH5Deltas was sufficient to recapitulate the effects of secreted ITIH5 on cell morphology, motility and metastasis. These data suggest that ITIH5 may suppress metastasis by an intracellular mechanism not predicted by previously published reports. Understanding how intracellular ITIH5 attenuates PDAC metastasis could reveal new elements of PDAC biology that could become future therapeutic targets for patients affected by this aggressive cancer.
Notlar:
School code: 0099
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(681716.1) | 681716-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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