Table 3.
Puzzling observational results under somatic mutation theory and key aspects of their explanations under the detached pericyte hypothesis.
| Puzzling observational results under the somatic mutation theory | Relevant information | Explanation under the detached pericyte hypothesis |
|---|---|---|
| Naked mole rats rarely develop cancer [45]. | Naked mole rat fibroblasts secrete HMH [46]. Genetic knock-down of HMH leads to tumors [46]. HMH dampens fibrosis [47, 48]. | HMH dampens fibrosis so reduces cancer risk. |
| Although both XP and CS involve defects in DNA repair that protect against sunlight, only XP patients have high skin cancer risk [49]. | Actinic keratosis is associated with tissue changes [50] and skin cancer [51]. Actinic keratosis appears in XP patients [52] but not in CS patients [53]. | Actinic keratosis is a marker for changes in ECM that lead to cancer. |
| Obesity increases cancer risk, but the mechanism is not known [54]. | Obesity induces fibrosis [55]. | Fibrosis leads to cancer. |
| Schistosomiasis is linked to bladder cancer, but the mechanism is not known [56]. | Flatworms cause schistosomiasis and lay eggs in the bladder causing fibrosis [57]. | Fibrosis leads to cancer. |
| Asbestos causes lung cancer, but the mechanism is not known [58]. | Asbestosis is associated with asbestos exposure and lung cancer [58]. | Fibrosis leads to cancer. |
| Smoking causes lung cancer, but the mechanism is not known [59]. | COPD is associated with lung cancer and airway scarring [60, 61]. Cigarette smoke modifies stromal fibroblasts in lung epithelium [62]. | Altered ECM from scarring and fibroblasts leads to cancer. |
| Some viruses cause cancer, but the mechanism is not known [63]. | Viruses are associated with apoptosis [64]. Dysregulation of apoptosis can lead to fibrosis [65]. Hepatitis B is associated with both liver fibrosis and cancer [66]. | Virus causes apoptosis which causes fibrosis and cancer. |
| Injected RSV yields tumors at the site of the injection [67]. | Vascular injury leads to pericyte detachment [12–15]. | Injection detaches pericytes. |
| Some childhood neuroblastomas spontaneously regress [68, 69]. | In one nodule, the neuroblastoma regressed to a scar [69]. | Altered ECM leads to cancer that regresses if ECM is normalized |
*
HMH=high-molecular mass hyaluronan. XP=Xeroderma pigmentosa. CS =Cockayne Syndrome. COPD=chronic obstructive pulmonary disease. RSV=Rous sarcoma virus. ECM=extracellular matrix.