Table 4.

Phenotypical consequences of collagen-binding integrin knockouts in mice.

Integrin subunit	Expression	Knockout phenotype	Pathologically challenged knockout phenotype	Cancer phenotype
α1	Endothelial cells, fibroblasts, pericytes, mesangial cells, bone marrow mesenchymal stem cells, hepatic stellate cells, chondrocytes, neural cells, Schwann cells, immune cells (285, 286)	No pronounced phenotype (286) moderate decrease in body weight, hypocellular dermis (287) aged-related osteoarthritis (288), retinal degeneration (289)	Reduced psoriasis (290) and inflammation (129), accelerated aging-dependent osteoarthritis (288), reduced bone fracture healing (291), increased glomerulosclerosis in diabetic mice (293), hepatic insulin resistance and decreased hepatic fat accumulation on a high fat diet (292)	Reduced tumor number and size, reduced angiogenesis and proliferation, increased apoptosis in models of non-small cell lung carcinoma α1-null mice (294, 295); overexpression in colorectal cancers and correlation with Myc oncogene; reduced angiogenesis, increased necrosis and low mitotic index in a xenograft model of colorectal cancers (296); reduced angiogenesis in an experimental breast cancer model (297); correlation with a poor patient outcome in melanoma (298, 299); gain of expression in oral squamous cell carcinomas, broncho-alveolar and gastric carcinomas (300–302)
α2	Epithelial cells, platelets/megakaryocytes, endothelial cells fibroblasts (303, 304)	Moderate phenotype in mammary gland morphogenesis (305, 306), adhesion defects for isolated platelets on collagen I (307), reduced age-related osteoporosis (308)	Increased neovascularization in wound healing (309), defects in age-related bone loss (308), decreased immune response to peritoneal Listera infection and reduced thrombi formation (239), decreased glomerulosclerosis upon renal injury (310), reduced inflammation and cartilage deterioration in rheumatoid arthritis (311), reduced inflammatory bowel disease (65)	Metastasis suppressor in the MMTV-neu mouse breast cancer model and correlation with patient outcome in breast and prostate cancers (312); impaired breast cancer metastasis in a xenograft model of MCF-7 cells interacting with platelets (313); reduced MMP13 expression by metastasizing cells to the bones in an experimental model of MDA-MB-231 breast cancer cells (314); impaired tumor angiogenesis in a melanoma xenograft model in a double knockout model (66); co-localization with E-cadherin and N-cadherin at tumor cell-cell contacts in primary and metastatic samples of melanoma (315); selective metastasis to the bones in prostate cancer (316); implication in doxorubicin-induced drug resistance in leukemia (317, 318); implication in other types of cancers, including pancreatic, colorectal, gastric and lung cancers, oral squamous cell carcinoma and T-cell acute lymphoblastic leukemia (319)
α10	Chondrocytes, mesenchymal stem cells, junctional fibroblasts (241, 320)	Mild chondrodysplasia (321), canine chondrodysplasia and limb dwarfism (322)	ND	Upregulation in malignant melanoma (323); overexpression in glioblastoma (324); high expression correlated with disease-specific death and distant metastasis in high-grade myxofibrosarcoma (325)
α11	Fibroblasts (cancer associated fibroblasts, myofibroblasts), mesenchymal stem cells (326–328)	Dwarfism, altered incisor tooth eruption, increased mortality and decreased IGF-1 serum levels (327, 329, 330)	Reduced wound strength and deposition of granulation tissue in wound healing (263), reduced cardiac fibrosis and left ventricular hypertrophy (331)	Decreased tumorigenicity of cancer cells (328) and matrix stiffness (332) in a challenged xenograft model of lung cancer; correlation with tumor progression and postoperative recurrence in non-small cell lung cancer (333); association with a pro-tumorigenic PDGFRβ-positive subset of cancer associated fibroblasts and correlation with a poor clinical outcome in breast cancer (280); correlation with aggressive phenotypes of breast cancer (334); decreased intratumoral interstitial fluid pressure and collagen structure in a challenged mouse tumor model (335)