Influence of cathepsin D expression in lung adenocarcinoma on prognosis: Possible importance of its expression in tumor cells and stromal cells, and its intracellular polarization in tumor cells

The aim of this study was to investigate the role of cathepsin D in colorectal cancer. For this purpose cathepsin D expression was evaluated by means of immunohistochemistry in stromal and tumor cells of 31 colorectal carcinomas and 29 adenomas. Cytoplasmic cathepsin D expression of tumor cells was present in 90.3% of the carcinoma cases and various degrees of stromal cell cathepsin D expression were present in all cases. In the adenomas, the epithelial cells and stromal cells expressed cathepsin D in 68.96% and 96.55% of cases, respectively. The staining intensity was always weaker in the adenomas. When the stromal and tumor cell cathepsin D expression in the adenocarcinoma and adenoma cases were compared, a statistically significant difference was observed in the staining of stromal cells. Furthermore, stromal cathepsin D expression in the adenocarcinomas was related to tumor stage when the carcinomas were divided into low and high stage. Cathepsin D expression in stromal cells may be an important indicator of poor prognosis in colorectal adenocarcinomas.

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Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative breast cancer

Human Pathology ◽

10.1016/s0046-8177(96)90214-2 ◽

1996 ◽

Vol 27 (9) ◽

pp. 890-895 ◽

Cited By ~ 38

Author(s):

Mehrdad Nadji ◽

Manuel Fresno ◽

Mehdi Nassiri ◽

Gregory Conner ◽

Agustin Herrero ◽

...

Keyword(s):

Breast Cancer ◽

Aggressive Behavior ◽

Tumor Cells ◽

Stromal Cells ◽

Cathepsin D ◽

Node Negative ◽

Node Negative Breast Cancer

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Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22041918 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1918

Author(s):

Mio Yamaguchi ◽

Kiyoshi Takagi ◽

Koki Narita ◽

Yasuhiro Miki ◽

Yoshiaki Onodera ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Tumor Progression ◽

Tumor Cells ◽

Cancer Progression ◽

Stromal Cells ◽

Human Breast Carcinoma ◽

Breast Cancer Patients ◽

Breast Carcinomas ◽

Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

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The dynamic behavior of lipid droplets in the pre-metastatic niche

Cell Death and Disease ◽

10.1038/s41419-020-03207-0 ◽

2020 ◽

Vol 11 (11) ◽

Author(s):

Chunliang Shang ◽

Jie Qiao ◽

Hongyan Guo

Keyword(s):

Tumor Cells ◽

Immune Cells ◽

Stromal Cells ◽

Lipid Droplets ◽

Metastatic Tumor ◽

Current Evidence ◽

Biological Functions ◽

Metastatic Niche ◽

Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

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Identification of the signature genes and network of Reactive Oxygen Species (ROS) related genes and DNA repair genes in Lung Adenocarcinoma (LUAD)

10.21203/rs.3.rs-323059/v1 ◽

2021 ◽

Author(s):

Ye Zhao ◽

Hai-Ming Feng ◽

Xiao-Ping Wei ◽

Wei-Jian Yan ◽

Bin Li ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Dna Repair ◽

Tumor Cell ◽

Lung Adenocarcinoma ◽

Tumor Cells ◽

Patient Survival ◽

Reactive Oxygen ◽

Dna Repair Genes ◽

Oxygen Species ◽

Repair Genes

Abstract Reactive Oxygen Species (ROS) are present in high amount in patients with tumors, and these ROS can kill and destroy tumor cells. Thus, tumor cells upregulate ROS-related genes to protect themselves and reduce their destruction. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. In this work, lung adenocarcinoma (LUAD) transcriptome data in the TCGA database was analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related genes and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related genes and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby increasing the growth of tumor cells and balancing the level of ROS, leading to tumor cell death and constant damage to the tumor cell repair system, thus prolonging patient survival. Thus, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX and PFKP), the risk score might be used as an independent prognostic factor in LUAD patients.

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High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

Disease Markers ◽

10.1155/2010/465040 ◽

2010 ◽

Vol 28 (3) ◽

pp. 167-183 ◽

Cited By ~ 4

Author(s):

Giuseppina Nicotra ◽

Federica Manfroi ◽

Carlo Follo ◽

Roberta Castino ◽

Nicola Fusco ◽

...

Keyword(s):

Clinical Outcome ◽

Tumor Cells ◽

Survival Probability ◽

Cathepsin D ◽

Rank Test ◽

Lysosomal Protease ◽

T Cell Lymphomas ◽

Kaplan Meier ◽

Punctate Pattern ◽

Hodgkin's Lymphomas

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases;p= 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases;p= 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test,p= 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.

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Down-regulated LncR-MALAT1 suppressed cell proliferation and migration by inactivating autophagy in bladder cancer

RSC Advances ◽

10.1039/c8ra04876b ◽

2018 ◽

Vol 8 (54) ◽

pp. 31019-31027

Author(s):

Jiude Qi ◽

Yanfeng Chu ◽

Guangyan Zhang ◽

Hongjun Li ◽

Dongdong Yang ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Lung Adenocarcinoma ◽

Tumor Cells ◽

Cell Proliferation And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna ◽

Proliferation And Migration

Long non-coding RNA-metastasis-associated lung adenocarcinoma transcript (LncR-MALAT) is highly expressed in a variety of tumors, which can affect the progression of tumor cells.

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Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

Frontiers in Immunology ◽

10.3389/fimmu.2021.784691 ◽

2021 ◽

Vol 12 ◽

Author(s):

Erwan Dumontet ◽

Stéphane J. C. Mancini ◽

Karin Tarte

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Tumor Cells ◽

Stromal Cells ◽

Therapeutic Option ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Niche Adaptation ◽

Functional Features

B-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches.

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The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors

Frontiers in Oncology ◽

10.3389/fonc.2021.723707 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wei Li ◽

Jin Yang ◽

Ping Zheng ◽

Haining Li ◽

Shaolin Zhao

Keyword(s):

Cancer Therapy ◽

Tumor Cells ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Chemotherapy Resistance ◽

Tissue Type ◽

Cell Contact ◽

Local Resident ◽

Anti Cancer ◽

Direct Cell

Cancer-associated mesenchymal stromal cells (CA-MSCs) have been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. However, very little is known about the origins and generating process of CA-MSCs, which may facilitate the identification of biomarkers for diagnosis or innovative targets for anti-cancer therapy to restrain the tumor growth, spread and chemotherapy resistance. Current evidences have indicated that both distally recruited and local resident MSCs are the primary origins of CA-MSCs. In a tissue type-dependent mode, tumor cells together with the TME components prompt the malignant transition of tumor “naïve” MSCs into CA-MSCs in a direct cell-to-cell contact, paracrine or exosome-mediated manner. In this review, we discuss the transition of phenotypes and functions of naïve MSCs into CA-MSCs influenced by tumor cells or non-tumor cells in the TME. The key areas remaining poorly understood are also highlighted and concluded herein.

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