In This Issue
In This Issue
Silencing of connexin 43 suppresses invasion, migration, and lung metastasis of rat hepatocellular carcinoma cells
Most deaths from cancer result from metastases that are resistant to conventional therapies. Metastasis is a multistep process, with multiple genes and factors regulating each stage. An improved understanding of the mechanisms of cancer metastasis is necessary for the development of treatments that prevent or target metastases. Ogawa and colleagues established six rat hepatocellular carcinoma cell lines, each with different metastatic potential to the lung following inoculation into the tail vein. The researchers analyzed factors that could play a role in attachment of circulating tumor cells to metastatic sites. One day after inoculation, lung metastatic foci occurred only with the highly metastatic cell lines with elevated connexin 43 expression. Transfection of an siRNA targeting connexin 43 suppressed in vitro invasion and migration and significantly reduced in vivo metastatic ability. The results suggest that connexin 43 may regulate tumor cell invasion and metastasis and is a potential therapeutic target for prevention of cancer metastasis.
α-Interferon modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine
Pancreatic cancer patients have a 5-year survival rate of only 5%. The poor prognosis of pancreatic cancer patients may result from the actions of cancer stem cells (CSCs), which can contribute to drug resistance and sustain tumor growth. Hayashi and colleagues investigated whether α-interferon (IFN-α) can modulate the chemosensitivity of a human pancreatic cell line to chemotherapies with gemcitabine (GEM). CD133 is a marker of CSCs in pancreatic cancer. CD133+ cells showed CSC-like properties including generation of spheres, high invasion ability, and high tumorigenesis. Gemcitabine efficiently acted on both CD133+ and CD133− S-phase cells, but CD133+ cells could escape the treatment by remaining in G0/G1 phase. α-Interferon modulated CD133+ cells from G0/G1 phase to S phase, resulting in accelerated apoptosis with GEM treatment. Combined IFN-α and GEM treatment also produced significant tumor suppression in vivo. The results suggest IFN-α could contribute to treatment of CD133+ cancer cells and, in combination with GEM, effectively treat pancreatic cancer stem-like cells.
Expression of GSTP1 predicts poor pathological complete response to neoadjuvant chemotherapy in estrogen receptor-negative breast cancer
Neoadjuvant chemotherapy (NAC) for primary breast cancer enhances the operability of cases of advanced tumors, and its use has become widespread. However, adverse effects of NAC are common and only 20–30% of patients show pathological complete response to NAC, which is associated with a better prognosis. Miyake and colleagues sought to determine predictive factors for response to NAC in order to avoid unnecessary use of the therapy in patients who are unlikely to benefit. The researchers studied the association of GSTP1 expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in primary breast cancer patients. Expression of GSTP1 was associated with a lower clinical response to P-FEC regardless of estrogen receptor (ER) status. Expression of GSTP1 was also associated with a lower pathological complete response rate in ER-negative but not ER-positive tumors. The authors suggest that GSTP1 expression may be useful for identification of ER-negative breast tumors that are unlikely to benefit from P-FEC treatment.