Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells

Tian, Chenxi; Huang, Ying; Clauser, Karl R.; Rickelt, Steffen; Lau, Allison N.; Carr, Steven A.; Heiden, Matthew G. Vander; Hynes, Richard O.

doi:10.1038/s41467-021-22490-9

Cited by 52 publications

(44 citation statements)

References 60 publications

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“…Tumors in SPARC -/- mice had decreased levels of collagen type I and III and higher levels of TAM-infiltration, which were associated with reduced survival and increased metastasis ( 170 ). Another study used mice with impaired pro-collagen processing to show that collagens produced selectively by the cancer cells had anti-tumorigenic effects ( 171 ).…”

Section: The Role Of Collagen For Immune Activity In Tumors In Vivomentioning

confidence: 99%

Immune Modulatory Properties of Collagen in Cancer

2021

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During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

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Section: The Role Of Collagen For Immune Activity In Tumors In Vivomentioning

confidence: 99%

Immune Modulatory Properties of Collagen in Cancer

2021

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“…Collagen I is among the most abundant collagen in PDAC stroma and is generally suggested to be responsible for most of the desmoplastic reaction and has been associated with reduced survival in PDAC patients (43)(44)(45). However, when C-terminal prodomains of collagen I are cleaved by procollagen Cproteinase activity, collagen I may restrain tumor growth (46,47). In addition, the presence of collagen I in the TME does not appear to inhibit T-cell infiltration (48), further suggesting the stroma has roles beyond a physical barrier.…”

Section: Collagens I Iii Iv and Vmentioning

confidence: 99%

The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies

2021

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Pancreatic ductal adenocarcinoma (PDAC) is notorious for a dense fibrotic stroma that is interlaced with a collagen-based extracellular matrix (ECM) that plays an important role in tumor biology. Traditionally thought to only provide a physical barrier from host responses and systemic chemotherapy, new studies have demonstrated that the ECM maintains biomechanical and biochemical properties of the tumor microenvironment (TME) and restrains tumor growth. Recent studies have shown that the ECM augments tumor stiffness, interstitial fluid pressure, cell-to-cell junctions, and microvascularity using a mix of biomechanical and biochemical signals to influence tumor fate for better or worse. In addition, PDAC tumors have been shown to use ECM-derived peptide fragments as a nutrient source in nutrient-poor conditions. While collagens are the most abundant proteins found in the ECM, several studies have identified growth factors, integrins, glycoproteins, and proteoglycans in the ECM. This review focuses on the dichotomous nature of the PDAC ECM, the types of collagens and other proteins found in the ECM, and therapeutic strategies targeting the PDAC ECM.

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“…All the chemicals used in this study were at the analytical reagent grades. BPsQDs were synthesized with the liquid exfoliation method, as reported in recent report (McAllaster & Cohen, 2011 ; Yun et al., 2017 ; Tian et al., 2021 ). In briefly, 20 mg of BPs powders were dispersed in 20 mL NMP, and the mixture was thereafter sonicated with a sonic tip at an ultrasonic frequency of 19–25 kHz for 4 h with 2 s duration plus the interval of 4 s at a power of 1200 W. Afterwards, the mixture was further sonicated overnight in an ice bath at a power of 300 W. Finally, BPQDs dispersed in supernatant were collected after centrifugations at 7000 rpm for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Black phosphorus conjugation of chemotherapeutic ginsenoside Rg3: enhancing targeted multimodal nanotheranostics against lung cancer metastasis

Xiong

Yuan

et al. 2021

Drug Delivery

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It is a significant challenge in lung cancer chemophotothermal (CPT) therapy to develop multifunctional theranostic nanoagent (MTN) for precise targeting and successful tumor treatments, especially for lung metastasis. To overcome this problem, we effectively design and construct multifunctional black phosphorus (BP) nanoagents, BPs/G-Rg3@PLGA. BPs quantum dots (BPsQDs) are co-loaded onto poly(lactic-co-glycolic acid) (PLGA) with subsequent conjugations of a cancer therapeutic compound, ginsenoside Rg3 (G-Rg3), in this composite nanoagent. The in vivo delivery findings suggest that BPs/G-Rg3@PLGA has an excellent affinity for primary tumors and metastatic lung tumors. Furthermore, when paired with near-light irradiation, BPs/G-Rg3@PLGA shows superior controllable CPT therapy synergetic therapeutics, significantly increasing photothermal tumor ablation effectiveness. Mechanistically, heating causes rapid G-Rg3 release from the non-complex, and thermal therapy induces apoptosis, culminating in the reduction of lung cancer metastasis. Additionally, in vivo and in vitro findings support the biocompatibility of BPs/G-Rg3@PLGA. This thesis identifies a versatile BPs-based MTN for lung cancer metastasis control.

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Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells

Cited by 52 publications

References 60 publications

Immune Modulatory Properties of Collagen in Cancer

Immune Modulatory Properties of Collagen in Cancer

The PDAC Extracellular Matrix: A Review of the ECM Protein Composition, Tumor Cell Interaction, and Therapeutic Strategies

Black phosphorus conjugation of chemotherapeutic ginsenoside Rg3: enhancing targeted multimodal nanotheranostics against lung cancer metastasis

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