Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression

Iwamoto, Chika; Ohuchida, Kenoki; Shinkawa, Tomohiko; Okuda, Sho; Otsubo, Yoshiki; Okumura, Takashi; Sagara, Akiko; Koikawa, Kazuhiro; Ando, Yuichi; Shindo, Koji; Ikenaga, Naoki; Nakata, Kohei; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Eto, Masatoshi; Akashi, Koichi; Nakamura, Masafumi

doi:10.1016/j.canlet.2021.04.013

Cited by 36 publications

(22 citation statements)

References 49 publications

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“…In addition, considering the significant positive correlation between the degree of FDG uptake and macrophage infiltration in the tumors, FDG uptake of BM could be affected by the metabolic activity of BM-derived macrophages [ 18 ]. BM-derived macrophages can convert to tumor-associated macrophages in the tumor microenvironment, which contributes to a favorable microenvironment for tumor growth [ 18 , 35 ]. In previous studies, increased myeloid-derived suppressor cells and tumor-associated macrophages were also significantly associated with poor response to treatment and worse survival in patients with pancreatic cancer [ 8 , 35 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…BM-derived macrophages can convert to tumor-associated macrophages in the tumor microenvironment, which contributes to a favorable microenvironment for tumor growth [ 18 , 35 ]. In previous studies, increased myeloid-derived suppressor cells and tumor-associated macrophages were also significantly associated with poor response to treatment and worse survival in patients with pancreatic cancer [ 8 , 35 , 36 , 37 ]. Based on these results, it is plausible that FDG uptake of BM has a significant association with OS in patients with pancreatic cancer as shown in our study, suggesting that FDG uptake of BM might be used to estimate host immune conditions in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, growing evidence has suggested that the host microenvironment plays an essential role in the growth and metastasis of cancer cells, as well as the biological characteristics of cancer cells [ 20 , 40 ]. Because immune cells derived from the BM such as myeloid-derived suppressor cells and macrophages significantly influence the host organ microenvironment, the degree of BM FDG uptake, which reflects the degree of production and metabolic activity of BM-derived immune cells, can be used to estimate the immune microenvironment of the host organ [ 17 , 18 , 35 , 41 ]. Hence, a prognostic model that combines tumor factors and BM imaging parameters that reflect host factors could improve the prediction of the prognosis of cancer patients when compared with a model only with tumor intrinsic factors.…”

Section: Discussionmentioning

confidence: 99%

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Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT

Lee

Park

Ahn

et al. 2021

Cancers

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The purpose of this study was to evaluate the prognostic significance of FDG uptake of bone marrow (BM SUV) and to investigate its role combined with radiomic features of primary tumors in improving the prediction of overall survival (OS) in patients with pancreatic cancer. We retrospectively enrolled 65 pancreatic cancer patients with staging FDG PET/CT. BM SUV and conventional imaging parameters of primary tumors including total lesion glycolysis (TLG) were measured. First-order and higher-order textural features of primary cancer were extracted using PET textural analysis. Associations of PET/CT parameters of bone marrow (BM) and primary cancer with OS were assessed. BM SUV as well as TLG and first-order entropy of pancreatic cancer were significant independent predictors of OS in multivariable analysis. A PET/CT scoring system based on the cumulative scores of these three independent predictors enabled patient stratification into three distinct prognostic groups. The scoring system yielded a good prognostic stratification based on subgroup analysis irrespective of tumor stage and treatment modality. BM SUV was an independent predictor of OS in pancreatic cancer patients. The PET/CT scoring system that integrated PET/CT parameters of primary tumors and BM can provide prognostic information in pancreatic cancer independent of tumor stage and treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT

Lee

Park

Ahn

et al. 2021

Cancers

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“…However, it has also been shown that adipose-derived mesenchymal stem cells can differentiate into CAF in vitro and in vivo (Miyazaki et al, 2020), (Miyazaki et al, 2021). Moreover, bone marrow-derived macrophages also can differentiate into CAF (Iwamoto et al, 2021). Whereas the diverse source of CAF may lead to functional differences, it is necessary to study PSC as a well-defined concept.…”

Section: Differentiation Mechanism Of Myofibroblastic and Inflammatory Pscmentioning

confidence: 99%

Heterogeneous Pancreatic Stellate Cells Are Powerful Contributors to the Malignant Progression of Pancreatic Cancer

Zhang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic cancer is associated with highly malignant tumors and poor prognosis due to strong therapeutic resistance. Accumulating evidence shows that activated pancreatic stellate cells (PSC) play an important role in the malignant progression of pancreatic cancer. In recent years, the rapid development of single-cell sequencing technology has facilitated the analysis of PSC population heterogeneity, allowing for the elucidation of the relationship between different subsets of cells with tumor development and therapeutic resistance. Researchers have identified two spatially separated, functionally complementary, and reversible subtypes, namely myofibroblastic and inflammatory PSC. Myofibroblastic PSC produce large amounts of pro-fibroproliferative collagen fibers, whereas inflammatory PSC express large amounts of inflammatory cytokines. These distinct cell subtypes cooperate to create a microenvironment suitable for cancer cell survival. Therefore, further understanding of the differentiation of PSC and their distinct functions will provide insight into more effective treatment options for pancreatic cancer patients.

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“…The most common cells in the tumor microenvironment (TME) are cancer associated fibroblasts (CAFs). They often stem from pancreatic stellate cells (PSCs) but can also arise from resident fibroblasts (Haber et al, 1999;Shek et al, 2002) and can be recruited from bone marrow derived stem cells (Marrache et al, 2008;Iwamoto et al, 2021). Upon injury to the tissue, caused by trauma or infection, these cells differentiate into myofibroblasts, which are rich in α-smooth muscle actin (α-SMA, ACTA2), and built up the major part of the extracellular matrix (ECM) (Haber et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

Gündel

Liu

Löhr

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

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Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression

Cited by 36 publications

References 49 publications

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT

Heterogeneous Pancreatic Stellate Cells Are Powerful Contributors to the Malignant Progression of Pancreatic Cancer

Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

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