Expression of the Serine Protease Kallikrein 7 and Its
Inhibitor Antileukoprotease Is Decreased in
Qiang Xuan, MD; Xiaoli Yang, MD; Linjian Mo, MD; Fengyu Huang, MD; Youhong Pang, MD; Min Qin, MD;
Zhiqiang Chen, MD; Min He, MD; Qi Wang, MD; Zeng-Nan Mo, MD
● Context.—Kallikreins are a subgroup of serine proteases showed protein expression of hK7 and ALP in benign pros-
with diverse physiologic functions. It has been conﬁrmed tate epithelial cells and prostate cancer cell lines.
that kallikrein 7 (KLK7 ) is differentially expressed in ovar- Results.—Semiquantitative polymerase chain reaction
ian and breast cancer. Antileukoprotease (ALP) has been examination revealed that the mRNA level of KLK7 and
shown to be a speciﬁc inhibitor of human kallikrein 7 ALP was signiﬁcantly decreased in prostate cancers com-
(hK7). Antileukoprotease overexpression is commonly as- pared with that in benign prostate epithelial cells (P
sociated with aggressive, high-risk, or metastatic cancer .001). Immunohistochemical expression of hK7 was ob-
served in prostate epithelial cells, whereas little or no stain-
originating from various organs.
ing was observed in prostate cancer. Western blot analysis
Objective.—To investigate the expression and potential
revealed that hK7 and ALP were decreased in malignant
role of hK7 and its inhibitor ALP in prostate cancer. prostate epithelium.
Design.—The mRNA expression of KLK7 and ALP tran- Conclusions.—Like hK7, ALP is down-regulated in pros-
script in benign prostate epithelial cells and prostate can- tate cancers, which begs the question of whether it re-
cers was evaluated by semiquantitative reverse transcrip- mains an effective inhibitor of hK7 or whether it is discor-
tion–polymerase chain reaction. We examined hK7 and dant in time or space and is ineffective as an inhibitor of
ALP protein expression by immunohistochemistry in 20 hK7. The function of KLK7 and ALP in prostate cancer
normal prostate tissues, 50 benign prostatic hyperplasia tis- should be further studied.
sues, and 103 prostate cancers. Western blot examination (Arch Pathol Lab Med. 2008;132:1796–1801)
T he extracellular matrix proteolysis accompanying tu-
mor invasion and metastasis is a highly complicated
process and probably involves a cascade of events requir-
that hK7 may degrade adhesive interactions between in-
dividual corneocytes in the stratum corneum that are the
primary substrate for cellular desquamation or skin shed-
ing a variety of proteases.1 In this process, protease plays ding.5 The fact that inhibition of hK7 prevents normal des-
a central role in paving the way for spreading tumor cells. quamation of skin cells suggested that hK7 may represent
The human kallikrein gene family is a subfamily of serine a potential therapeutic target to inhibit the spread or me-
proteases and is located at chromosome locus 19q13.3- tastasis of carcinoma cells. Whether hK7 has a similar
q13.4. In recent years, 15 of the tissue kallikrein family function in prostate is worth studying.
genes have been identiﬁed and cloned. Human kallikrein Antileukoprotease (ALP), also known as secretory leu-
7 (hK7) was ﬁrst found in the human stratum corneum kocyte proteinase inhibitor, has been identiﬁed as a potent
and with a possible involvement in desquamation.2 There inhibitor of leukocyte chymotrypsin, trypsin, elastase, and
is now increasing evidence that many kallikrein family cathepsin G6 and plays a signiﬁcant role in protection
genes are related to human malignancies.3,4 We have found against neutrophil proteases during inﬂammatory re-
kallikrein 7 (KLK7) was upregulated in prostate epithelial sponses.7,8 The hK7-dependent desquamation of skin cells
cells cocultured with prostate ﬁbroblasts compared with can be inhibited by ALP.9 This serine protease inhibitor is
epithelial cells cultured separately. It has been suggested produced and released into mucus by secretory cells in
the prostate, parotid, bronchus, cervix, and testis.6 Anti-
leukoprotease has a local protective function against pro-
Accepted for publication April 15, 2008.
From the Institute of Urology, the First Afﬁliated Hospital (Drs Xuan, teolytic degradation of the male reproductive tract tis-
Yang, L. Mo, Huang, Pang, Qin, Chen, and Z.-N. Mo), the Laboratory sues10 and cervical gland. Several studies have reported
Center For Medical Science (Dr He), and the Afﬁliated Tumor Hospital increased ALP expression in ovarian cancer tissues and in
(Dr Wang), Guangxi Medical University, Nanning, China the serum of patients with non–small cell lung cancer.11–13
The authors have no relevant ﬁnancial interest in the products or Shigemasa et al14 also have identiﬁed that ALP, a peptide
companies described in this article.
Reprints: Zeng-Nan Mo, MD, Institute of Urology, The First Afﬁliated inhibitor of hK7, is highly overexpressed in ovarian tumor
Hospital of Guangxi M