Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

Abstract

Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and ⁄ or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg ⁄ 70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95 ± 0.04 to 4.63 ± 0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies. (Cancer Sci 2010; 101: 2105-2109 M ammary serpin (maspin), a serine proteinase inhibitor, has been reported to prevent ⁄ control breast cancer.( 1) This protein (42 kDa) is reported to be synthesized abundantly in normal mammary epithelial cells through the expression of maspin mRNA.(2,3) However, the synthesis of the protein is reported to progressively decrease with the progression of breast cancer.(2,3) Exogenously administered maspin in an animal model has been shown to reduce the growth and metastasis of breast cancer as well as to block tumor motility and invasion, (4,5) and the effect of maspin was reported to be reversed by the use of antimaspin antibody.(6) Considering the anticancer properties of maspin, it is possible to suggest that the protein plays a critically important role in the prevention of metastasis as well as in the development of breast cancer.It has been reported that the synthesis of this protein under physiological conditions is regulated by insulin-induced nitric oxide (NO) synthesis, and the impaired maspin synthesis in breast cancer (2,3) was related to the impairment of insulinreceptor interaction in the malignant cells, leading to impaired NO synthesis.(7) Maspin production in human breast cancer can be restored to normal ranges by using aspirin, which stimulates NO synthesis independently of the insulin receptor both in the case of malignant breast cancer cells in vitro, and in breast cancer patients who ingest the compound orally.(8) This effect of aspirin, resulting in the stimulation of NO synthesis in various cells, has been reported to be independent of the well-known effect of aspirin on the inhibition of prostaglandin synthesis. (9) Breast cancer is well known for its pr...

Aspirin use and breast cancer risk: a meta-analysis

“…Maspin has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of aspirin by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production [59]. Several limitations needed to be discussed in this metaanalysis.…”

Clinical evidence of the relationship between aspirin and breast cancer risk (Review)

“…Thus, the lack of expression of maspin in breast cancer has been suggested to indicate the presence of an aggressive and metastatic tumor (36). Studies have revealed that ingestion of aspirin increases the levels of serum nitric oxide (NO) and maspin, both of which inhibited the growth of breast cancer cells in vitro, as well as invasion and metastatic processes in an animal model (9,38). This finding suggests that aspirin participates in the restoration of maspin synthesis at any stage of the disease, and also that maspin presents beneficial effects at any stage of tumoral progression.…”

“…Regarding the possible anti-metastatic effect of aspirin, it was demonstrated that the daily ingestion of aspirin in patients previously treated with standard therapies indeed reduces metastasis, assigning this effect to the maspin protein (38). Maspin is a serine protease inhibitor of 42 kDa synthesized abundantly in normal mammary epithelial cells, and it has been shown that the expression of this protein is reduced in patients with breast cancer.…”

“…An epidemiologic example of this previously mentioned concept, is a study carried out in India, where the effect of aspirin and the incidence of metastasis in BC patients was determined (38). In this work, 35 women participated, and the age range was from 41 to 64 years.…”

Aspirin use and survival after the diagnosis of breast cancer: a population-based cohort study

“…An indirect effect of aspirin on mammary serpin (maspin) has been implicated in the prevention and control of breast cancer (Zou et al , 1994) and in an animal model by restoring nitrous oxide synthesis, increasing maspin production (Bhattacharyya et al , 2010). Overexpression of PTGS-2 in tumours has also been linked to promoting angiogenesis and inhibiting apoptosis (Sheng et al , 1998; Rozic et al , 2001), further implicating that aspirin could prevent growth, metastasis and recurrence.…”