Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis

Nakajima, Takahito; Uehara, Takeshi; Iwaya, Mai; Matsuda, Kazuyuki; Wada, Megumi; Nagaya, Tadanobu; Ehara, Takehito; Ota, Hiroyoshi

doi:10.1016/j.prp.2022.154190

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…Thus, an EMT‐associated gene expression signature in TB, including repressors of E‐cadherin and β‐catenin, has also been investigated in the context of TB 32 . Many proteins have been shown to be indicators of the formation of TB and survival 33–35 . Emerging studies have shown that the number of TB cases is negatively associated with T‐lymphocyte infiltration 7,20 .…”

Section: Discussionmentioning

confidence: 99%

High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

Liang,

Jie,

Xie

et al. 2024

Clin & Trans Imm

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ObjectivesEmerging evidence has demonstrated that tumour budding (TB) is negatively associated with T‐lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically ‘hot’ TB remain poorly understood.MethodsWe quantified the number of TB by haematoxylin–eosin (H&E) sections and the densities of CD3+ and CD8+ T‐lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T‐lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB‐positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed.ResultsIn a CRC cohort of 351 cases, low‐grade TB was associated with high CD3+ and CD8+ T‐cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB‐grade and T‐lymphocyte infiltration. In 278 TB‐positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low‐grade TB and positively associated with high CD3+ and CD8+ T‐cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease‐free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T‐lymphocyte infiltration.ConclusionsKRT17 can be employed as a new indicator for distinguishing different immunological TBs.

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Section: Discussionmentioning

confidence: 99%

High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

Liang,

Jie,

Xie

et al. 2024

Clin & Trans Imm

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“…The reciprocal crosstalk between TAMs and cancer cells via OPN/CD44 axis advances the tumorigenicity through activation of JNK pathway in colorectal carcinoma [29]. Similarly, Nakajima et al showed that TAM derived OPN acts as a key regulator of cancer progression through interacting with CD44v6 in colorectal cancer [132]. Kale et al demonstrated that tumor-derived OPN promotes macrophage-dependent tube formation ability of HUVEC by inducing Cox-2 expression in macrophages via ERK/p38-dependent signalling pathway in melanoma [56].…”

Section: Role Of Opn In Tam-mediated Tumor Progressionmentioning

confidence: 97%

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Panda,

Mishra,

Nath

et al. 2024

Preprint

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Tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cell, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs are crucial for enhancing the treatment outcome and reducing the burden of toxicity. In this review, we provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we have dissected the signalling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancement in role of various splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSCs enhancement, immunomodulation, metastasis, chemoresistance, metabolic reprogramming and further suggest that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

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“…CD44v6, a functional variant of CD44, was overexpressed on cancer cells located in the invasive front of colorectal cancer, and SPP1-expressing TAMs interacted with CD44v6-postive cancer cells, indicating the significance of SPP1/CD44v6 binding in cancer progression [ 97 ]. Among CD44 variants, CD44v9 is considered to be associated with cancer stem cells in various cancers, but few reports have described the interactions between CD44v9 and SPP1.…”

Section: Significance Of Spp1 Expression In Tams In Malignant Tumors ...mentioning

confidence: 99%

The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

Matsubara

Yano

Pan

et al. 2023

Cancers

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Macrophages are a representative cell type in the tumor microenvironment. Macrophages that infiltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related to invasion, metastasis, and immunosuppression, and an increased density of TAMs is associated with a poor clinical course in many cancers. Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional secreted phosphorylated glycoprotein. Although SPP1 is produced in a variety of organs, at the cellular level, it is expressed on only a few cell types, such as osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid cells, and mononuclear cells. SPP1 is also expressed by cancer cells, and previous studies have demonstrated correlations between levels of circulating SPP1 and/or increased SPP1 expression on tumor cells and poor prognosis in many types of cancer. We recently revealed that SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma. In this review, we summarize the significance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of monocyte-derived TAMs in lung adenocarcinoma. Several studies have shown that the SPP1/CD44 axis contribute to cancer chemoresistance in solid cancers, so the SPP1/CD44 axis may represent one of the most critical mechanisms for cell-to-cell communication between cancer cells and TAMs.

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Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis

Cited by 8 publications

References 39 publications

High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

High KRT17 expression in tumour budding indicates immunologically ‘hot’ tumour budding and predicts good survival in patients with colorectal cancer

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

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