Claudins as markers for early detection, diagnosis, prognosis and as targets of therapy for breast and metastatic brain or bone cancer
Methods of diagnosis, prognosis, and treatment of breast cancer, and of metastatic brain cancer, are provided The diagnostic and prognostic methods involve the immunohistochemical detection of the level of expression of the proteins claudin 1, 3, 4, and 7 in tissue or cell samples. Claudins 1 and 7 are underexpressed in the majority of breast cancers, and claudins 3 and 4 are overexpressed. The methods of treatment involve the use of Clostridium perfringens enterotoxin (or a variant thereof) to lyse metastatic cancer cells in the brain and bone that overexpress claudins 3 and 4.
1. A method for diagnosing metastatic breast, colon or lung cancer in a patient in need thereof, comprising the steps of
determining a level of expression of claudin 3 or claudin 4 or both claudins 3 and 4 in cells obtained from brain or bone tissue from said patient, and
assessing whether claudin 3 or claudin 4 or both claudins 3 and 4 are expressed in said cells at a level that is higher than a level of expression in disease-free individuals, wherein metastasis to brain or bone tissue is implicated when claudin 3 or claudin 4 or both claudins 3 and 4 are expressed at or above said level that is higher than a level of expression in disease-free individuals.
2. The method of claim 1 , wherein said step of determining is carried out by exposing said cells to at least one antibody recognizing claudin 3 or claudin 4 or both claudin 3 and claudin 4.
3. The method of claim 1 , wherein said tissue is a brain or bone biopsy tissue sample.