Microenvironmental changes in the progression from adenocarcinoma in situ to minimally invasive adenocarcinoma and invasive lepidic predominant adenocarcinoma of the lung

Naito, Masahito; Aokage, Keiju; Saruwatari, Koichi; Hisakane, Kakeru; Miyoshi, Tomohiro; Hishida, Tomoyuki; Sato, Masato; Kojima, Masaru; Kuwata, Takeshi; Fujii, Satoshi; Ochiai, Atsushi; Sato, Yukitoshi; Tsuboi, Masahiro; Ishii, Genichiro

doi:10.1016/j.lungcan.2016.07.024

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…Subtype C CAFs (where PDPN is one of the top genes) appear to have an immunogenic profile, which, in part, may explain the good prognosis observed in the ICGC and IHC analysis. Some studies in other cancer types support this hypothesis, showing a positive association between PDPN-positive CAFs and lymphocyte and macrophage infiltration [38][39][40], as well as tumours with a high mutation burden [41,42], suggesting that PDPN expression may be an indicator of immunogenic tumours. We summarise these findings in Figure 6H.…”

Section: Discussionmentioning

confidence: 90%

Inter‐ and intra‐tumoural heterogeneity in cancer‐associated fibroblasts of human pancreatic ductal adenocarcinoma

Neuzillet

Tijeras‐Raballand²,

Ragulan

et al. 2019

The Journal of Pathology

230

261

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Cancer‐associated fibroblasts (CAF) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Stromal heterogeneity may explain differential pathophysiological roles of the stroma (pro‐ versus anti‐tumoural) in PDAC. We hypothesised that multiple CAF functional subtypes exist in PDAC, that contribute to stromal heterogeneity through interactions with cancer cells. Using molecular and functional analysis of patient‐derived CAF primary cultures, we demonstrated that human PDAC‐derived CAFs display a high level of inter‐ and intra‐tumour heterogeneity. We identified at least four subtypes of CAFs based on transcriptomic analysis, and propose a classification for human PDAC‐derived CAFs (pCAFassigner). Multiple CAF subtypes co‐existed in individual patient samples. The presence of these CAF subtypes in bulk tumours was confirmed using publicly available gene expression profiles, and immunostainings of CAF subtype markers. Each subtype displayed specific phenotypic features (matrix‐ and immune‐related signatures, vimentin and α‐smooth muscle actin expression, proliferation rate), and was associated with an assessable prognostic impact. A prolonged exposure of non‐tumoural pancreatic stellate cells to conditioned media from cancer cell lines (cancer education experiment) induced a CAF‐like phenotype, including loss of capacity to revert to quiescence and an increase in the expression of genes related to CAF subtypes B and C. This classification demonstrates molecular and functional inter‐ and intra‐tumoural heterogeneity of CAFs in human PDAC. Our subtypes overlap with those identified from single‐cell analyses in other cancers, and pave the way for the development of therapies targeting specific CAF subpopulations in PDAC. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 90%

Inter‐ and intra‐tumoural heterogeneity in cancer‐associated fibroblasts of human pancreatic ductal adenocarcinoma

Neuzillet

Tijeras‐Raballand²,

Ragulan

et al. 2019

The Journal of Pathology

230

261

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“…Since laminin-5 contains Epidermal Growth Factor (EGF)-like repeats in the short arms, it may interact with one of its many potential ligands to mediate diverse cellular functions, including activation of EGFR signaling, similar to integrins (Engel, 1996). Being an extracellular matrix protein, laminin-5 plays an important role in cell migration (Fukai et al, 2005) and may be relevant for disease progression from adenocarcinoma in situ (AIS) to lepidic predominant adenocarcinoma (LPA) of the lung (Naito et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer

Yang¹,

Teng²,

Han³

et al. 2017

Genet. Mol. Res.

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Lung cancer is the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide. Fascin-1 and laminin-5 were associated with the invasiveness and prognoses of several cancers. The expression and the serum levels of fascin-1 and laminin-5 in patients with non-small cell lung cancer (NSCLC) were analyzed in this study. The expression of fascin-1 and laminin-5 were examined in 378 patients and their serum level was measured in 154 patients. The health of all patients was followed post-surgery. The expression of fascin-1 (P = 0.000) and lanminin-5 (P = 0.001) and the serum levels of fascin-1 (P = 0.015) and laminin-5 (P = 0.046) were related to the relapse of patients with NSCLC. Both serum levels and expression of fascin-1 and laminin-5 can be used to effectively evaluate the prognoses of patients with NSCLC.

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“…29 The current World Health Organization classification scheme proposes that the new adenocarcinoma in situ and minimally invasive carcinoma categories represent a stepwise progression of Lepþ adenocarcinoma. Naito and colleagues 11 reported that this morphologic progression is associated with elevated cancer cell-specific expression of invasion-related molecules, as well as increased recruitment of tumor-promoting stromal cells. Thus, Lepþ adenocarcinomas may slowly acquire malignant potential as their invasive components undergo stepwise changes (ie, ''multistage carcinogenesis'') ( Figure 3).…”

Section: Discussionmentioning

confidence: 99%

“…To research the tumor promoting stromal cells, we investigated PDPNþ cancer-associated fibroblast (CAFs) and CD204þ tumorassociated macrophages (TAMs). 11,14,15 Then after washing them with PBS again, they were incubated with EnVision (Agilent Technologies, Santa Clara, Calif) for 1 hour at room temperature. After washing them with PBS, the color reaction was performed with diaminobenzidine.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…Given the influence of stromal cells on clinical tumor features, characterization of stromal cell phenotypes may improve our understanding of patient prognosis. [8][9][10][11] Typical adenocarcinoma cases contain both lepidic and nonlepidic (invasive) components (lepidic-growth positive [Lepþ] adenocarcinomas). Computed tomography (CT) findings of these cases often include both ground-glass opacity (GGO) in the periphery and a solid component in the center.…”

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confidence: 99%

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Differences of tumor microenvironment between stage I lepidic-positive and lepidic-negative lung adenocarcinomas

Katsumata

Aokage

Miyoshi

et al. 2018

The Journal of Thoracic and Cardiovascular Surgery

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Microenvironmental changes in the progression from adenocarcinoma in situ to minimally invasive adenocarcinoma and invasive lepidic predominant adenocarcinoma of the lung

Cited by 21 publications

References 35 publications

Inter‐ and intra‐tumoural heterogeneity in cancer‐associated fibroblasts of human pancreatic ductal adenocarcinoma

Inter‐ and intra‐tumoural heterogeneity in cancer‐associated fibroblasts of human pancreatic ductal adenocarcinoma

Clinical significance of fascin-1 and laminin-5 in non-small cell lung cancer

Differences of tumor microenvironment between stage I lepidic-positive and lepidic-negative lung adenocarcinomas

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