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Cited by 32Pancreatic and Hepatic Oncology ResearchCancer Cells and MetastasisMechanisms of cancer metastasis

The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights

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Joshi, Vidhu B., Gutierrez Ruiz, Omar L., Razidlo, Gina L.·2023·Cancers
DOI 10.3390/cancers15072169PMC PMC10093482
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality worldwide. This is largely due to the lack of routine screening protocols, an absence of symptoms in early-stage disease leading to late detection, and a paucity of effective treatment options. Critically, the majority of patients either present with metastatic disease or rapidly develop metastatic disease. Thus, there is an urgent need to deepen our understanding of metastasis in PDAC. During metastasis, tumor cells escape from the primary tumor, enter the circulation, and travel to a distant site to form a secondary tumor. In order to accomplish this relatively rare event, tumor cells develop an enhanced ability to detach from the primary tumor, migrate into the surrounding matrix, and invade across the basement membrane. In addition, cancer cells interact with the various cell types and matrix proteins that comprise the tumor microenvironment, with some of these factors working to promote metastasis and others working to suppress it. In PDAC, many of these processes are not well understood. The purpose of this review is to highlight recent advances in the cell biology of the early steps of the metastatic cascade in pancreatic cancer. Specifically, we will examine the regulation of epithelial-to-mesenchymal transition (EMT) in PDAC and its requirement for metastasis, summarize our understanding of how PDAC cells invade and degrade the surrounding matrix, and discuss how migration and adhesion dynamics are regulated in PDAC to optimize cancer cell motility. In addition, the role of the tumor microenvironment in PDAC will also be discussed for each of these invasive processes.

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  • PDAC cells acquire pro-metastatic traits that enable them to disseminate and spread before primary tumour formation.

    “PDAC cells acquire pro‐metastatic traits that enable them to disseminate and spread before primary tumour formation”

    From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in <scp>2D</scp> and <scp>3D</scp> Cell Culture Models (2024) · cites this paper as [39]

    The Introduction says evidence suggests PDAC cells can acquire pro-metastatic traits and disseminate even before the primary tumor forms. The claim presents that possibility as an established occurrence, omitting the source’s uncertainty. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PDAC patients present with liver (76%-80%), peritoneum (48%) or lung (45%) metastasis at diagnosis.

    “resulting in PDAC patients presenting with liver (76%–80%), peritoneum (48%) or lung (45%) metastasis at diagnosis [39, 40]”

    From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in <scp>2D</scp> and <scp>3D</scp> Cell Culture Models (2024) · cites this paper as [39]

    The Introduction states that some PDAC patients present with metastatic disease, supporting the general point about metastasis at diagnosis. Neither it nor the other passages found gives the claimed liver (76%–80%), peritoneum (48%), or lung (45%) percentages. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Joshi, V. B., Gutierrez Ruiz, O. L., & Razidlo, G. L.
Affiliations
  • Mayo Clinic (US)
  • Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
Corresponding author
Razidlo, Gina L.
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2023-04-06
Volume
15
Issue
7
Pages
2169
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers15072169
PMC
PMC10093482
OpenAlex
W4362669695
Cited by
32
References
6
Citations by year
2026: 11 · 2025: 6 · 2024: 10 · 2023: 5
FWCI
1.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • The Mayo Clinic Center for Biomedical Discovery (P30CA015083)
  • The Mayo Clinic Cancer Center (P30CA015083)
  • The Mayo Clinic Graduate School of Biomedical Sciences (P30CA015083)
  • The Mayo Clinic Division of Gastroenterology &amp; Hepatology (P30CA015083)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords
pancreatic ductal adenocarcinoma, metastasis, epithelial-mesenchymal transition, tumor invasion, extracellular matrix degradation, tumor cell migration, cell adhesion, tumor microenvironment, basement membrane invasion, tumor cell motility

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