FAPESP Researchers Uncover Hidden Pathways in Pancreatic Cancer Metastasis

Breakthrough in Pancreatic Cancer Research: FAPESP-Funded Discovery at USP

Brazilian scientists supported by the São Paulo Research Foundation (FAPESP, or Fundação de Amparo à Pesquisa do Estado de São Paulo) have made a pivotal discovery illuminating how pancreatic cancer spreads through hidden biological pathways. Researchers at the University of São Paulo's (USP) Center for Research on Inflammatory Diseases (CRID) identified the critical role of pancreatic stellate cells in producing periostin, a protein that remodels surrounding tissue to enable perineural invasion—a key driver of metastasis in pancreatic ductal adenocarcinoma (PDAC), the most common and lethal form of pancreatic cancer. 51 50

This finding, detailed in a study published in the journal Molecular and Cellular Endocrinology, offers new hope for targeted therapies that could disrupt early tumor spread, potentially improving survival rates for patients worldwide, including in Brazil where the disease claims thousands of lives annually. 99

Pancreatic Ductal Adenocarcinoma: A Global and Brazilian Health Challenge

Pancreatic ductal adenocarcinoma (PDAC) originates in the glandular tissues of the pancreas and accounts for approximately 90% of all pancreatic cancer cases. Unlike other cancers, PDAC is notoriously aggressive, with symptoms often appearing only at advanced stages, making early detection rare. Globally, the World Health Organization reports around 510,000 new cases and nearly as many deaths each year, underscoring why mortality rates closely mirror incidence. 51

In Brazil, the National Cancer Institute (INCA) estimates about 11,000 new diagnoses and 13,000 deaths per year, with long-term survival—defined as five years post-diagnosis—achieved in only around 10% of cases. Projections from INCA for 2023-2025 indicate a steady rise in cancer burdens, including pancreatic types, driven by aging populations and lifestyle factors. This stark reality highlights the urgency of research like that from FAPESP-funded teams at USP, which could pave the way for breakthroughs benefiting Brazilian healthcare systems and higher education institutions training the next generation of oncologists. 79

For academics and researchers in Brazil, understanding PDAC's regional impact is crucial. Institutions like USP Ribeirão Preto play a central role, fostering collaborations that translate lab findings into clinical applications while creating opportunities in research jobs focused on oncology.

Decoding Perineural Invasion: The 'Highway' for Cancer Spread

Perineural invasion (PNI) occurs when cancer cells infiltrate and travel along nerves surrounding the pancreas, acting as a 'highway' for distant metastasis. This process is present in more than 50% of early-stage PDAC cases, often undetected until surgery, and correlates strongly with pain, recurrence, and poor prognosis. 52

Step-by-step, PNI unfolds as follows:

• Tumor cells trigger intense extracellular matrix (ECM) remodeling through interactions with stromal cells.
• Cancer cells adhere to nerve sheaths, degrading myelin via enzymes.
• Cells migrate along nerves toward lymphatics or bloodstream, seeding metastases in liver, lungs, or peritoneum.
• This invasion sparks a desmoplastic reaction—dense fibrosis that hardens tissue, shields the tumor, and blocks chemotherapy drugs.

Such mechanisms explain PDAC's resistance to standard treatments like surgery, radiation, and chemotherapy, emphasizing why FAPESP's investment in spatial transcriptomics at CRID is transformative for Brazilian higher education research.

Pancreatic Stellate Cells and Periostin: Unmasking the Mechanism

Pancreatic stellate cells (PSCs), normally quiescent support cells in the pancreas, activate in response to tumor signals. The USP study revealed PSCs expressing high levels of periostin (POSTN)—a matricellular protein—enriched in PNI-positive tumors. Periostin binds integrins on cancer cells, reorganizing the ECM with collagens and metalloproteinases to create invasion paths. 99

Lead researcher Helder Nakaya explains: "Periostin participates in this remodeling, paving the way for tumor cells to invade." Co-author oncologist Pedro Luiz Serrano Uson Junior adds that blocking these cells could prevent early invasiveness. 51

Analysis of ~60,000 single cells from 24 PDAC biopsies showed POSTN+ PSCs clustered near invasive fronts, coordinating with tumor-derived ANXA1 and PSC SPP1/PLAU signaling to myeloid cells—a multicellular axis driving PNI.Read the full FAPESP report. 51

This discovery positions periostin as a biomarker and target, with implications for researchers pursuing postdoc positions in stromal biology at Brazilian universities.

Cutting-Edge Methods Powering the Discovery

The CRID team leveraged single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics on public datasets, integrating data via Seurat and CellChat tools. This high-resolution mapping distinguished PSC subtypes and their proximity to nerves, revealing insights missed in bulk analyses. 99

Such bioinformatics prowess, honed at USP, exemplifies FAPESP's role in equipping São Paulo universities with world-class tech, attracting global talent for research assistant jobs.

FAPESP's Vital Support for Oncology Innovation in Brazil

FAPESP, as Brazil's premier research funder, backs centers like CRID through its Research, Innovation, and Dissemination Centers (RIDCs) program. This enables multidisciplinary teams at USP to tackle grand challenges like cancer, fostering PhD scholarships, postdocs, and international collaborations. 53

Between 2007-2016, Brazil invested heavily in oncology via FAPESP and peers, yielding projects like this PDAC study. For aspiring academics, FAPESP's Young Investigator Grants offer pathways to lead labs in São Paulo.Explore FAPESP cancer research.

• Annual funding up to BRL 8 million per RIDC.
• Thousands of scholarships for grad students in oncology.
• Partnerships with global institutions for tech transfer.

This ecosystem bolsters Brazil's higher education, linking discovery to careers via platforms like AcademicJobs Brazil.

Treatment Horizons: Targeting Periostin and Beyond

With no PNI-specific therapies yet, the study spotlights periostin inhibitors. Ongoing trials in breast and colorectal cancers test anti-POSTN antibodies, potentially adaptable for PDAC. Precision medicine could profile tumors for PSC activity, guiding personalized regimens. 63

Challenges include fibrosis blocking drugs, but combining periostin blockade with stroma-modulators shows promise in models. For Brazilian patients, this could alleviate INCA's burden, while opening clinical research jobs.

Career Opportunities in Brazilian Cancer Research

USP's success underscores vibrant prospects for researchers. CRID regularly posts postdocs in immunology and cancer, funded by FAPESP. Brazil's universities seek experts in transcriptomics, with roles in faculty positions at USP, UNICAMP, and more.

Explore career advice or university jobs in Brazil's thriving oncology sector.

Future Outlook: From Pathways to Prevention

Looking ahead, this FAPESP discovery could spur trials by 2027, integrating AI for PSC targeting. Broader impacts include multi-cancer applications and bolstering Brazil's research GDP contribution. Stakeholders—from INCA clinicians to USP students—anticipate actionable insights.Access the study. 99

In summary, FAPESP researchers' elucidation of periostin-driven PNI redefines PDAC metastasis, promising better outcomes and enriching higher education. For jobs advancing this field, visit rate professors, higher ed jobs, or career advice.