Anticancer drugs kill tumor cells and increase host anti-tumor immunity. Interestingly, gemcitabin (Gem) and 5-fluorouracil (5-FU), widely used anticancer drugs, lead to IL-1beta secretion releasing cathepsin B which activates Nlrp3 inflammasome in myeloid derived suppressor cells (MDSCs). MDSC derived IL-1beta enhance secretion of IL-17 by CD4+ T cells. This mechanism limits the antitumor efficacy of the drugs and promotes tumor growth.
Cathepsin B ; Cathepsins ; Fluorouracil ; Interleukin-17 ; T-Lymphocytes

Adenocarcinoma, Mucinous ; enzymology ; pathology ; Cathepsin B ; metabolism ; Cathepsin D ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness

PURPOSE: The purpose of this study is to evaluate the expression of E-cadherin and cathepsin-B in prostatic carcinomas and correlate with the Gleason grades. MATERIALS AND METHODS: The expressions of E-cadherin and cathepsin B were examined by the immunohistochemical technic using the antibodies against the E-cadherin and cathepsin B on the paraffin block sections of 56 prostatic carcinomas with evaluation of Gleason grading. RESULTS: E-cadherin expression in normal epithelium was membranous intercellular expression and those of prostate carcinomas were aberrant expressions such as negative expression or cytoplasmic presentation. The expressivity of the E-cadherin according to the progression of the Gleason grading revealed negative membranous expression and tendency of gradual increase of aberrant expression. The normal prostate and BPH revealed expression of cathepsin B mostly in the basal layers of acini as cytoplasmic reaction and the stromal macrophages and microvessel wall also showed positive expression. The prostatic carcinoma showed cytoplasmic positivity in the cancer cells and the expression rate was increased from Gleason grade 2 to Gleason grade 4. But the Gleason grade 5 tissue revealed decreased or negative expression. The Gleason grade 4, especially in the invasive cells and invasive edges, revealed the most intense and frequent expression of cathepsin B and this findings were consistent with the nonnal function of the cathepsin B as a protease degrading the extracellular matrix proteins. CONCLUSION: E-cadherin expression was aberrant after Gleason grade 6 related with high histologic grades. It is suggested that the E-cadherin expression could tell the potential cancer progression as a tumor suppression factor. The cathepsin B was most strongly expressed in basal cells of the benign prostatic acini and the cancer nests of Gleason grade 4, which tells the possibility that cathepsin B could be a marker of basocellular differentiation and of assessing stromal invasion of prostatic carcinomas.
Antibodies ; Cadherins* ; Cathepsin B* ; Cathepsins* ; Cytoplasm ; Epithelium ; Extracellular Matrix Proteins ; Macrophages ; Microvessels ; Neoplasm Grading ; Paraffin ; Prostate

Cancer is the result of damage to the genetic system, i.e., dysfunction of the DNA repair system, resulting in dysregulated expression of various molecules, leading to cancer formation, migration, and invasion. In cancer progression, several proteases play a critical role in metastasis; however, their biological mechanism in cancer metastasis is not clearly understood. Among these proteases, cathepsins are a family of lysosomal proteases found in most animal cells. Cathepsins have an important role in protein turnover of mammalian, and are classified into 15 types based on their structure as serine (cathepsin A and G), aspartic (cathepsin D and E), and cysteine cathepsins (cathepsin B, C, F, H, K, L, O, S, V, X, and W). Cysteine cathepsins appear to accelerate the progression of human and rodent cancers, which can be a biomarker of the potency of malignancy or metastasis in mammalian. Overexpression of cyteine cathepsins causes the activation of angiogenesis promoting factor, whereas their downregulation reduces the angiogenesis of cancer progression. Under physiological conditions, cysteine cathepsins are essential in inflammation, infection, and cancer development. Activity of cysteine proteases, i.e., cathepsin B, is required for cancer progression or metastasis. Elevation of cysteine cathepsin is associated with cancer metastasis, angiogenesis, and immunity. Therefore, in this review, we suggest that cysteine cathepsin may be an anticancer target of strong clinical interest, although the exact mechanism of cathepsins in cancer metastasis is under investigation.
Animals ; Cathepsin B ; Cathepsins ; Cysteine ; Cysteine Proteases ; DNA Repair ; Down-Regulation ; Humans ; Inflammation ; Neoplasm Metastasis ; Peptide Hydrolases ; Rodentia ; Serine

The invasion of basement membrane is one of the most important steps for tumor dissemination. Invasive human bladder tumor cells have the ability to degrade basement membrane, especially laminin with cysteine proteinase, cathepsin B which is mainly located in plasma membrane of tumor cell. Cathepsin B was assayed by spectrofluorometer in plasma membrane of human invasive bladder tumor cell line J82. The activities of cathepsin B were 0.98+/-0.14 nmol/ mg/min in plasma membrane fraction. E-64, a synthetic cysteine proteinase inhibitor decrease the activities of cathepsin B to 0.45+/-0.06 nmol/mg/min, 0.30+/-0.06 nmol/mg/min, 0.17+/-0.04 nmol/mg/min, 0.12+/-0.02 nmol/mg/min and 0.09+/-0.01 nmol/mg/min at the concentrations of 20pM, 40pM, 60pM, 80pM and 100pM, respectively. E-64 could prevent the degradation of human basement membrane laminin by the plasma membrane fraction of J82 which was shown in Western blot using polyclonal rabbit antilaminin antibody. In an in vitro model of tumor invasion, membrane invasion culture system (MICS), the numbers of J82 cells which had invaded Matrigel were 4.7+/-2.2 cells/field, 13.1+/-5.6 cells/field an 28.0+/-5.3 cells/field with 25ug Matrigel after 2 hours, 4 hours and 6 hours of incubation period. Migrated tumor cells were 31.2+/-7.3 cells/field. 28.0+/-5.3 cells/field, 18.2+/-3.1 cells/field and 10.6+/-4.6 cells/field with 0ug, 25ug, 50ug and 100ug of the amount of Matrigel, respectively. The number of migrated tumor cells was decreased proportionally to the increase of Matrigel amount. When 25ug Matrigel was used for 6 hours in MICS the invaded tumor cells were 28.0+/-5.3 cells/field, 18.3+/-6.0cells/field, 13.1+/-6.0 cells/field, 12.4+/-3.9 cells/field and 5.5+/-2.3 cells/ field after adding E-64 at the concentration of 0uM, 50uM, 100uM, 200uM and 400uM, respectively. The findings suggest that cathepsin B, cysteine proteinase may play an important role in the progression of superficial bladder tumor into invasive bladder tumor and E-64, cysteine proteinase inhibitor, may inhibit the invasion of superficial bladder tumor.
Basement Membrane ; Blotting, Western ; Cathepsin B ; Cell Line ; Cell Membrane ; Cysteine Proteases ; Humans* ; Laminin ; Membranes ; Urinary Bladder Neoplasms* ; Urinary Bladder*

BACKGROUND: Cathepsin is associated with tumorigenesis, tumor invasion and metastasis through its ability to induce degradation of extracellular matrix components. METHODS: To investigate the correlation between cathepsin expression and tumor progression, invasion depth or nodal metastasis, immunohistochemical staining for cathepsins B, H and L were done on 20 hyperplastic polyps, 48 adenomas, and 67 adenocarcinomas of the colon. Evaluation of the expression of cathepsins B, H and L was based on the percentage of neoplastic cells that stained positive for any given cathepsin. RESULTS: Cathepsin B expression was significantly higher in adenocarcinomas than adenomas (29.33 vs 5.48%), but was not associated with the degree of differentiation, depth of invasion and nodal status of the tumors. Expression of cathepsins H and L was absent or low in both adenomas and adenocarcinomas. CONCLUSIONS: We suggest that cathepsin B is involved in progression of a subset of colonic adenomas, while cathepsins H and L are not.
Adenocarcinoma ; Adenoma ; Cathepsin B ; Cathepsins ; Cell Transformation, Neoplastic ; Colon ; Extracellular Matrix ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial ; Polyps

Aberrations on the short arm of chromosome 8 (8p) are frequently observed in several human cancers. In this study, 20 squamous cell carcinoma (SCC) specimens from the tongue were examined in order to evaluate the role of 8p in SCC of the tongue. Microsatellite analysis using 14 markers demonstrated two commonly deleted regions (CDRs) on 8p. Reverse transcription-polymerase chain reaction (RT-PCR) revealed frequent down-regulation of the FEZ1 gene, mapped to 8p22, and frequent over-expression of the cathepsin B gene, mapped to 8p-21-22. These results suggested that genetic aberrations are involved in the development of SCC of the tongue. However, no significant relationship was observed to be established between the genetic alterations and clinicopathological features. Thus, further investigation is necessary in order to clarify the clinical role of 8p in carcinoma of the tongue.
Arm ; Carcinoma, Squamous Cell ; Cathepsin B ; Chromosomes, Human, Pair 8 ; Down-Regulation ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; Tongue

<b>OBJECTIVEb>To investigate the expression of cathepsin B (CatB) in colorectal cancer tissues and serum levels of CatB in patients with colorectal carcinoma and to study the association of CatB expression with lymph node and li ver metastasis.

<b>METHODSb>Immunohistochemistry was used to detect CatB expression in tissues, and enzyme linked immunosorbent assay was applied to test CatB levels in peripheral vein blood in 83 patients with colorectal cancer.

<b>RESULTSb>The expression rates of CatB in primary lesions, normal colon mucosa, lymph node metastases and hepatic metastases were 56.6%, 31.3%, 88.4%, 85.0% respectively. The positive rates of CatB in primary lesions, hepatic and lymph node metastases were higher than that in normal mucosa (chi (2)=45.6124, P< 0.01). The CatB expression rates in lymph node and hepatic metastases were higher than that in primary lesions chi (2)=11.5982, 4.3747, P< 0.05). The positive rate of CatB was higher in Dukes C and D tumors than that in Dukes A and B tumors (chi (2)=18.8871, 25.1650, P< 0.01), higher in poorly differentiated and mucous adenocarcinomas than that in well-moderately differentiated adenocarcinomas chi (2)=14.2338, P< 0.05). The mean serum level of CatB in 83 patients with colorectal cancer was (5.9+/- 2.9) ng/ml, higher than (2.3+/- 1.1) ng/ml in the controls of 30 healthy volunteers (t=6.6975, P< 0.01). The serum level of CatB in the patients with Dukes C, D stages were higher than that with Dukes A, B stages.

<b>CONCLUSIONSb>Enhanced expression of CatB in colorectal cancer tissues is associated with tumor infiltration and metastasis. Monitoring serum CatB level in patients with colorectal cancer is important in the prediction and diagnosis of lymph node and hepatic metastasis,and valuable for evaluation of the therapeutic effect.

Adult ; Aged ; Cathepsin B ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging

OBJECTIVE: To study the expression of cathepsin-B and -D in different time point after traumatic brain injury. METHODS: Traumatic brain injury (TBI) model was established on rats, cathepsin-B and cathepsin-D immunofluorescence staining and confocal microscope analysis were performed. Positive cells were counted by confocal microscope and image analysis techniques were used to determine the morphological changes in each group. RESULTS: Immunofluorescence staining results showed that cathepsin-B was activated 1 hour after TBI while cathepsin-D was not activated until 12hour after TBI. Both of them got to their peak during 4 to 8days, and kept a high level of activating 32days after TBI. Cathepsin-B and -D positive cells did not merge with caspase-3 positive cells until 6 h after TBI. CONCLUSION Cathepsin-B and -D could be the diagnostic markers of TBI and can estimating time course of lateral TBI. They blocked caspase-3 activation at the beginning period after TBI and started to promote cell death with caspase-3 6 h after TBI.
Animals ; Brain/pathology* ; Brain Injuries/pathology* ; Caspase 3/metabolism* ; Cathepsin B/metabolism* ; Cathepsin D/metabolism* ; Disease Models, Animal ; Forensic Pathology ; Hippocampus/pathology* ; Immunohistochemistry ; Lysosomes ; Male ; Neurons/metabolism* ; Rats ; Rats, Sprague-Dawley ; Time Factors

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant α-GalCer. As results, TgCPC1 DNA vaccine with or without adjuvant α-GalCer showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and IFN-γ in the spleen compared to controls (PBS, pEGFP-C1, and α-Galcer). Upon challenge infection with tachyzoites of T. gondii (RH), pCPC1/α-Galcer immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and α-Galcer). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.
Animals ; B-Lymphocytes ; Cathepsin C* ; Cathepsins* ; DNA* ; Epitopes, T-Lymphocyte ; Immunoglobulin G ; Interleukin-2 ; Mice* ; Peptide Hydrolases ; Spleen ; Toxoplasma* ; Toxoplasmosis* ; Vaccines, DNA*