Table 2.
Expression and significance of cathepsins in tumor cells and stromal cells
| Type of cathepsin | Type of tumor | Type of samples and expression changes | Outcomes | Reference |
|---|---|---|---|---|
| Cathepsin B | Laryngeal cancer | Tissues (↑) Cell line (HEP-2) | Cathepsin B is positively correlated with migration, invasion, and proliferation | [350] |
| Gastric cancer | Tissues (↑) Patient serum (↑) | Serum cathepsin B is positively associated with late stage and poor prognosis | [351] | |
| Breast cancer | Tissues (↑) | Cathepsin B is a prognostic marker for indication of recurrence | [352] | |
| Non-small cell lung cancer | Tissues (↑) | Activity of cathepsin B is significantly higher in tumor | [353] | |
| Melanoma | Patient serum (↑) | Serum cathepsin B indicates metastatic melanoma and shorter overall survival | [354] | |
| Colorectal cancer | Tissues (↑) | Elevated cathepsin B (from TAMs) is correlated with metastases | [355] | |
| Glioblastoma | Cell line (SNB19) | Cathepsin B and MMP-9 promote tumor invasion, growth, and angiogenesis | [356] | |
| Prostate cancer | Cell line (PC3 and DU145) | Cathepsin B and MMP-9 are positively correlated with cell survival, invasion, and angiogenesis | [357] | |
| Pancreatic islet cell carcinoma | Tissues from mouse model (RIP1-Tag2) (↑) | Cathepsin B promotes tumor formation, angiogenesis, invasion, and proliferation | [358] | |
| Meningioma | Tissues | Cathepsin B is expressed in endothelium and microvessels | [359] | |
| Cathepsin C | Colorectal cancer | Cell lines (HCT-116, HT29, and KM12C) | Cathepsin C inhibition blocks autophagy and induced ER stress and apoptosis | [360] |
| Renal cell carcinoma | Cell lines (786-O and A-498) | Timosaponin AIII suppresses cathepsin C expression, thus inhibiting cell migration and invasion | [361] | |
| Non-small cell lung cancer | Tissues (↑) | High cathepsin C expression is correlated with tumor recurrence | [362] | |
| Hepatocellular carcinoma | Tissues (↑) Cell lines (SK-HEP-1, SMMC-7721, hepg2, MHCC-97H, Hep3B, and PLC/PRF/5) | Cathepsin C promotes proliferation and metastasis | [363] | |
| Pancreatic islet cell carcinoma | Tissues from mouse model (RIP1-Tag2) (↑) | Cathepsin C is expressed in tumor tissues | [358] | |
| Squamous carcinoma | Tissues from mouse model (K14-HPV16) (↑) | Cathepsin C facilitates squamous carcinogenesis process | [364] | |
| Tongue cancer | Tissues | Cathepsin C is expressed in tongue cancer | [365] | |
| Cathepsin F | Osteosarcoma | Cell lines (saos-2, lm5, and lm-7) | Cathepsin F is negatively correlated with metastasis | [366] |
| Gastric cancer | Tissues (↓) Cell lines (SGC7901, BGC823, MGC803, HGC27, AGS, and MKN45) (↓) | Cathepsin F is negatively correlated with proliferation and cell survival | [367] | |
| Cervical cancer | Tissues (↑) Cell lines (hela, calo, INBL, siha, and caski) (↑) | Cathepsin F is involved in pathogenesis of cervical cancer | [368] | |
| Cathepsin H | Hepatocellular carcinoma | Cell line (HepG2) | Cathepsin B is expressed in HepG2 | [369] |
| Pancreatic islet cell carcinoma | Mouse model (RIP1-Tag2) | Cathepsin H promotes tumor growth, angiogenesis, and decreases apoptosis | [370] | |
| Lung cancer | Tissues (↓) Patient serum (↑) | Serum cathepsin H is higher in patients | [371] | |
| Glioblastoma | Tissues (↑) Cell lines (u251, uwr1, and uwr2) | Cathepsin H promotes tumor cell invasion | [372] | |
| Prostate cancer | Cell line (PC-3) | Cathepsin H mediates migration and invasion | [373] | |
| Melanoma | Patient serum (↑) | Cathepsin H indicates shorter overall survival rates | [354] | |
| Basal cell carcinoma | Tissues (↑) | Cathepsin H (from peritumoral cells) promotes invasion of tumor | [374] | |
| Cathepsin K | Glioblastoma | Expression data from database (↑) | Cathepsin K is not correlated with survival | [375] |
| Breast cancer | Cell lines (MDA-MB-231 and SK-BR-3) | Cathepsin K promotes proliferation and metastasis | [376] | |
| Oral squamous cell carcinoma | Tissues (↑) | Cathepsin K (from stromal and tumor cells) indicates lymph node metastasis, perineural invasion, and poor survival | [377] | |
| Colorectal cancer | Tissues (↑) Cell line (MC38) | Cathepsin K (from tumor cells) promotes invasion, M2-like polarization of TAMs, and poor outcomes | [378] | |
| Prostate cancer | Tissues (↑) Cell lines (lncap, C4-2B, and PC3) (↑) | Cathepsin K promotes cell invasion | [379] | |
| Skull base chordoma | Tissues (↑) | Cathepsin K is correlated with reduced progression-free survival | [380] | |
| Ovarian cancer | Tissues (↑) Cell line (OV-2008) | Cathepsin K promotes metastasis and poor prognosis | [381] | |
| Melanoma | Tissues (↑) | Cathepsin K is an independent predictor of metastasis | [382] | |
| Gastric cancer | Tissues (↑) | Cathepsin K promotes tumor recurrence | [383] | |
| Cathepsin L | Breast cancer | Cell line (MDA-MB-468 and MCF-7) | Cathepsin L is located in nucleus with help of Snail | [384] |
| Glioma | Cell line (U87 and U251) | Cathepsin L promotes cell survival, migration, and invasion | [385] | |
| Cervical cancer | Tissues (↑) Cell lines (MS751, Caski, hela, C33A, and siha) | Cathepsin L facilitates migration and invasion of cancer cells | [386] | |
| Ovarian cancer | Tissues (↑) Cell lines (SKOV3 and SKOV3/TAX) | Cathepsin L promotes cell proliferation, migration, invasion, and paclitaxel resistance | [387] | |
| Gastric cancer | Tissues (↑) | High cathepsin L is correlated with metastases, poor differentiation, and diffuse histotype | [388] | |
| Colorectal cancer | Tissues (↑) Cell lines (SW480, SW620, SW1116, SW837, and SW948) | Cathepsin L is inversely associated with survival | [389] | |
| Non-small cell lung cancer | Cell lines (A549 and H1299) | Mutated K-ras promotes cathepsin L expression in irradiation treated cells resulting in enhanced invasion and migration | [390] | |
| Pancreatic cancer | Tissues (↑) patient serum (↑) | High serum cathepsin L is associated with poor prognosis | [391] | |
| Melanoma | Cell line (mv3) | Cathepsin L is detected in cell supernatants | [392] | |
| Cathepsin O | Breast cancer | Tissues | A Cathepsin O mutation is correlated with shorter disease-free and overall survival | [393] |
| Cathepsin S | Prostate cancer | Tissues (↑) Mouse model (TRAMP) | Cathepsin S (from TAMs) is expressed in castration-resistant, poor differentiation, or high Gleason grade tumor | [394] |
| Gastric cancer | Tissues (↑) Patient serum (↑) Cell lines (SGC7901, MKN45, AGS, MGC803) (↑) | Cathepsin S is correlated with higher TNM, later stage, and poorer overall survival | [395] | |
| Hepatocellular carcinoma | Cell line (MHCC97-H) | Cathepsin S inhibition induces apoptosis and chemosensitivity | [396] | |
| Triple-negative breast cancer | Cell lines (MDA-MB-231 and MCF-7) | Cathepsin S promotes cell growth and metastasis | [397] | |
| Papillary thyroid cancer | Expression data from database (↑) | Cathepsin S is a predictive marker for progression and prognosis | [398] | |
| Non-small cell lung cancer | Patient serum | Cathepsin S activity is detected in patient serum | [399] | |
| Colorectal cancer | Tissues (↑) Cell line (SL4) | Cathepsin S is associated with M2-like TAMs, higher histologic grade, and later clinical stage | [257] | |
| Cathepsin V/L2 | Colorectal cancer | Tissues (↑) | Cathepsin L2 is expressed in colorectal cancer | [400] |
| Breast cancer | Tissues (↑) | High cathepsin V predicts poor prognosis | [401] | |
| Thymic carcinoma | Tissues | Cathepsin V inhibits tumor recurrences | [200] | |
| Endometrial cancer | Tissues (↑) | Cathepsin V expression is correlated with growth regulatory gene expression | [402] | |
| Cathepsin W | – | – | No research about cathepsin W in tumor was found | – |
| Cathepsin X | Breast cancer | Cell line (MCF-7) | Cathepsin X participates in EMT | [195] |
| Gastric cancer | Tissues Cell line (N87) | Cathepsin X inhibits G1 arrest and apoptosis | [403] | |
| Colorectal cancer | Tissues | Increased cathepsin X (from TAMs) is found during tumorigenesis; however, loss of cathepsin X is correlated with tumor progression | [198] | |
| Prostate cancer | Tissues (↑) | Cathepsin X is expressed in prostate cancer and prostatic intraepithelial neoplasia | [404] | |
| Glioblastoma | Expression data from database (↑) | High cathepsin X is correlated with poor survival | [375] | |
| Cathepsin A | Prostate cancer | Tissues (↑) Cell lines (pc3 and du145) | Cathepsin A promotes proliferation, EMT, and tumorigenesis | [405] |
| Melanoma | Tissues (↑) Cell lines (B78, MmB16, and B16F10) | High cathepsin A activity was detected in melanoma lesions | [406, 407] | |
| Lung cancer | Expression data from database (↑) Cell line (A549) | Cathepsin A promotes cell proliferation, migration, and invasion | [408] | |
| Colorectal cancer | Tissues (↑) Cell lines (HCT116 and lovo) | High cathepsin A is associated with lymph node and liver metastasis | [409] | |
| Breast cancer | Tissues (↑) | High cathepsin A indicates poor prognosis and shorter recurrence-free interval | [410] | |
| Cathepsin G | Acute myeloid leukemia | Primary patient samples | Cathepsin G is a marker for poor survival | [411] |
| Tongue squamous cell carcinoma | Tissues | Cathepsin G is expressed in peri-tumoral stroma | [412] | |
| Acute lymphoblastic leukemia | Primary patient samples Cell lines (SUP-B15, SB, RS4;11, NALM6, Raji, and T2) | Cathepsin G is a poor prognosticator | [413] | |
| Glioblastoma | Tissues | Cathepsin G is expressed in the microvasculature | [414] | |
| Meningioma | Tissues | Cathepsin G is expressed in the interstitium | [359] | |
| Cathepsin D | Bladder cancer | Tissues | Cathepsin D is highly expressed in some tissue | [415] |
| Osteosarcoma | Tissues (↑) | Cathepsin D is a biomarker for osteosarcomas and pulmonary metastases | [416] | |
| Breast cancer | Tissues (↑) Cell lines (MDA-MB-231) | High cathepsin D is correlated with shorter recurrence-free survival | [417] | |
| Endometrial cancer | Patient serum (↑) | Cathepsin D and IgG was detected in patients | [418] | |
| Hepatocellular carcinoma | Patient serum (↑) | Cathepsin D is detected in patient serum | [419] | |
| Prostate cancer | Cell line (PC-3) | Cathepsin D fosters cell proliferation and invasion | [420] | |
| Nasopharyngeal carcinoma | Tissues cell lines (6-10B, 5-8F, CNE2, and CNE1) | Down-regulated cathepsin D indicates poor histological differentiation, while up-regulated cathepsin D indicates metastasis and poor prognosis | [421] | |
| Pancreatic cancer | Cell line (MIApaca2) | Cathepsin D and pro-cathepsin D promote cancer cell dissemination | [422] | |
| Non-small cell lung cancer | Tissues | Cathepsin D together with caspase 3− or p53+ are predictor for tumor node metastasis and lymph node metastasis, respectively | [423] | |
| Gastric cancer | Tissues | Cathepsin D participates in cancer metastasis | [383] | |
| Squamous cell carcinoma | Tissues (↑) | Cathepsin D is intensively expressed in poorly differentiated tissues | [424] | |
| Melanoma | Tissues (↑) | Cathepsin D is associated with tumor development | [425] | |
| Colorectal cancer | Patient serum (↑) | Cathepsin D is detected in patient serum | [426] | |
| Ovarian cancer | Tissues (↑) | Higher cathepsin D is expressed in more serous ovarian carcinoma. Cathepsin D in tumor epithelial cells may be beneficial prognostic factor | [427] | |
| Meningioma | Tissues | Cathepsin D is expressed in endothelium and microvessels | [359] | |
| Cathepsin E | Pancreatic cancer | Tissues (↑) | Cathepsin E is detected in pancreatic cancer | [428] |
| Esophageal cancer | Tissues (↑) | Barrett’s esophagus possesses higher cathepsin E than normal tissues. Esophageal cancer shows lower cathepsin E than Barrett’s esophagus but higher than normal tissues | [199] | |
| Bladder cancer | Tissues | High cathepsin E is correlated with better progression-free survival | [201] | |
| Gastric cancer | Tissues (↑) | Cathepsin E is a marker of signet-ring cell carcinoma and gastric differentiation | [429] | |
| Breast cancer | Patients serum | Cathepsin E is associated with favorable prognostic outcomes | [202] |
↑ upregulation, ↓ downregulation