Transcript analyses of stromal cell derived factors (SDFs): SDF-2, SDF-4 and SDF-5 reveal a different pattern of expression and prognostic association in human breast cancer.
Stromal derived factors, SDFs, are a loosely defined group of molecules that may be generated by stromal cells. Two of the stromal derived factors, SDF-1 and SDF-4 belong to the chemokine family. Other SDFs, such as SDF-2 and SDF-5 are not well defined and their biological functions are less known. Although SDF-1 and its receptor have been strongly indicated in the progression of various cancers including breast cancer, little is known with regard to the role of other SDFs in malignant conditions including breast cancer. In the present study, we analysed the pattern of expression of SDF-2, SDF2-like-1, SDF-4 and SDF-5 in breast cancer tissues and cells, at transcript and protein levels. It was found that SDF-2, SDF2-L1, SDF-4, and SDF-5 were ubiquitously expressed in various cancer cell lines. However, in clear contrast to SDF-1 whose over-expression has been shown to be linked to a poor clinical outcome, the present study provides evidence that the opposite appear to be true for SDF-2/SDF2-L1, SDF-4 and SDF-5. Significantly low levels of SDF-2 and SDF-4 were seen in patients with poor clinical outcome (with metastatic disease and death as a result of breast cancer, p<0.05, and p<0.01 respectively), when compared with patients who remained disease-free. SDF2-L1 and SDF-5 showed a similar trend. SDF-2 and SDF-L1 were also independent prognostic indicators (p=0.047 and p=0.012, respectively). It is concluded that SDF-2, SDF-4 and SDF-5 are expressed in mammary tissues and cells and that a reduced level of SDF-2, SDF2-L1 and SDF-4 are associated with a poor clinical outcome. These SDFs thus have prognostic value and warrant further investigation in their biological functions and clinical value.
Kang
Hua
H
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Escudero-Esparza
Astrid
A
Douglas-Jones
Anthony
A
Mansel
Robert E
RE
Jiang
Wen G
WG
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016019:Survival Analysis; D000094742:Secreted Frizzled-Related Proteins
D002135:Calcium-Binding Proteins; D019743:Chemokines, CXC; D006023:Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C102467:SDF2 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C422105:SDF2L1 protein, human; C099100:SDF4 protein, human